Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

Biogerontology

Volumn 16, Issue 2, 2015, Pages 147-185

  Smith, J A ^a,b   Leonardi, T ^a,b,c   Huang, B ^a,b   Iraci, N ^a,b   Vega, B ^a,b   Pluchino, S ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b University of Cambridge   (United Kingdom)

^c WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

Aging; Drug delivery; Exosomes; Extracellular vesicles; Nanomedicine; Neurodegeneration

Indexed keywords

AGING; ANIMAL; BIOLOGICAL MODEL; BRAIN; BRAIN DISEASE; CELL COMMUNICATION; EXOSOME; HUMAN; METABOLISM; PHYSIOLOGY;

AGING; ANIMALS; BRAIN; BRAIN DISEASES; CELL COMMUNICATION; EXTRACELLULAR VESICLES; HUMANS; MODELS, BIOLOGICAL;

EID: 84939887131     PISSN: 13895729     EISSN: 15736768     Source Type: Journal    
DOI: 10.1007/s10522-014-9510-7     Document Type: Review

References (389)

1. Agarwal A, Asthana A, Gupta U, Jain NK (2008) Tumour and dendrimers: a review on drug delivery aspects. J Pharm Pharmacol 60(6):671–688. doi:10.1211/jpp.60.6.0001
2. Aguzzi A, Rajendran L (2009) The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 64(6):783–790. doi:10.1016/j.neuron.2009.12.016
3. Ahmed F, Pakunlu RI, Brannan A, Bates F, Minko T, Discher DE (2006) Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. J Control Release 116(2):150–158. doi:10.1016/j.jconrel.2006.07.012
4. Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, Samiei M, Kouhi M, Nejati-Koshki K (2013) Liposome: classification, preparation, and applications. Nanoscale Res Lett 8(1):102. doi:10.1186/1556-276X-8-102
5. Akers JC, Gonda D, Kim R, Carter BS, Chen CC (2013) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 113(1):1–11. doi:10.1007/s11060-013-1084-8
6. Alais S, Simoes S, Baas D, Lehmann S, Raposo G, Darlix JL, Leblanc P (2008) Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles. Biol Cell 100(10):603–615. doi:10.1042/bc20080025
7. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, Wade-Martins R (2009) LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 18(21):4022–4034. doi:10.1093/hmg/ddp346
8. Alhasan AH, Patel PC, Choi CH, Mirkin CA (2014) Exosome encased spherical nucleic acid gold nanoparticle conjugates as potent microRNA regulation agents. Small 10(1):186–192. doi:10.1002/smll.201302143
9. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48. doi:10.1016/j.addr.2012.09.037
10. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10(5):619–624. doi:10.1038/ncb1725
11. Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJ, Cooper JM (2011a) Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 42(3):360–367. doi:10.1016/j.nbd.2011.01.029
12. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011b) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345. doi:10.1038/nbt.1807
13. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJA (2011c) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345
14. Andreola G, Rivoltini L, Castelli C, Huber V, Perego P, Deho P, Squarcina P, Accornero P, Lozupone F, Lugini L, Stringaro A, Molinari A, Arancia G, Gentile M, Parmiani G, Fais S (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 195(10):1303–1316
15. Antonyak MA, Li B, Boroughs LK, Johnson JL, Druso JE, Bryant KL, Holowka DA, Cerione RA (2011) Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. Proc Natl Acad Sci USA 108(12):4852–4857. doi:10.1073/pnas.1017667108
16. Arnold PY, Mannie MD (1999) Vesicles bearing MHC class II molecules mediate transfer of antigen from antigen-presenting cells to CD4 + T cells. Eur J Immunol 29(4):1363–1373
17. Arumugam K, Subramanian GS, Mallayasamy SR, Averineni RK, Reddy MS, Udupa N (2008) A study of rivastigmine liposomes for delivery into the brain through intranasal route. Acta Pharm 58(3):287–297. doi:10.2478/v10007-008-0014-3
18. Aushev VN, Zborovskaya IB, Laktionov KK, Girard N, Cros MP, Herceg Z, Krutovskikh V (2013) Comparisons of microRNA patterns in plasma before and after tumor removal reveal new biomarkers of lung squamous cell carcinoma. PLoS One 8(10):10. doi:10.1371/journal.pone.0078649
19. Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 32(3–4):623–642. doi:10.1007/s10555-013-9441-9
20. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14(7):677–685. doi:10.1038/ncb2502
21. Bakhti M, Winter C, Simons M (2011) Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J Biol Chem 286(1):787–796. doi:10.1074/jbc.M110.190009
22. Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, Alao H, Kodys K, Szabo G (2012) Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 56(5):1946–1957. doi:10.1002/hep.25873
23. Banigan MG, Kao PF, Kozubek JA, Winslow AR, Medina J, Costa J, Schmitt A, Schneider A, Cabral H, Cagsal-Getkin O, Vanderburg CR, Delalle I (2013) Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS One 8(1):e48814. doi:10.1371/journal.pone.0048814
24. Bard MP, Hegmans JP, Hemmes A, Luider TM, Willemsen R, Severijnen LA, van Meerbeeck JP, Burgers SA, Hoogsteden HC, Lambrecht BN (2004) Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am J Respir Cell Mol Biol 31(1):114–121. doi:10.1165/rcmb.2003-0238OC
25. Barenholz Y (2012) Doxil(R)—the first FDA-approved nano-drug: lessons learned. J Control Release 160(2):117–134. doi:10.1016/j.jconrel.2012.03.020
26. Batagov AO, Kuznetsov VA, Kurochkin IV (2011) Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles. BMC Genom 12(Suppl 3):S18. doi:10.1186/1471-2164-12-S3-S18
27. Batist G, Sawyer M, Gabrail N, Christiansen N, Marshall JL, Spigel DR, Louie A (2008) A multicenter, phase II study of CPX-1 liposome injection in patients (pts) with advanced colorectal cancer (CRC). J Clin Oncol 26(15):4108
28. Bedford P, Garner K, Knight SC (1999) MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed leukocyte reactions. Int Immunol 11(11):1739–1744. doi:10.1093/intimm/11.11.1739
29. Bellingham SA, Coleman BM, Hill AF (2012a) Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res 40(21):10937–10949. doi:10.1093/nar/gks832
30. Bellingham SA, Guo BB, Coleman BM, Hill AF (2012b) Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front Physiol 3:124. doi:10.3389/fphys.2012.00124
31. Belting M, Wittrup A (2008) Nanotubes, exosomes, and nucleic acid-binding peptides provide novel mechanisms of intercellular communication in eukaryotic cells: implications in health and disease. J Cell Biol 183(7):1187–1191. doi:10.1083/jcb.200810038
32. Bereczki E, Re F, Masserini ME, Winblad B, Pei JJ (2011) Liposomes functionalized with acidic lipids rescue Abeta-induced toxicity in murine neuroblastoma cells. Nanomedicine 7(5):560–571. doi:10.1016/j.nano.2011.05.009
33. Bevers EM, Comfurius P, Dekkers DW, Zwaal RF (1999) Lipid translocation across the plasma membrane of mammalian cells. Biochim Biophys Acta 1439(3):317–330. doi:10.1016/S1388-1981(99)00110-9
34. Bhatia D, Surana S, Chakraborty S, Koushika SP, Krishnan Y (2011) A synthetic icosahedral DNA-based host–cargo complex for functional in vivo imaging. Nat Commun 2:339. doi:10.1038/ncomms1337
35. Bianco F, Pravettoni E, Colombo A, Schenk U, Moller T, Matteoli M, Verderio C (2005) Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J Immunol 174(11):7268–7277
36. Bianco F, Perrotta C, Novellino L, Francolini M, Riganti L, Menna E, Saglietti L, Schuchman EH, Furlan R, Clementi E, Matteoli M, Verderio C (2009) Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J 28(8):1043–1054. doi:10.1038/emboj.2009.45
37. Bieda K, Hoffmann A, Boller K (2001) Phenotypic heterogeneity of human endogenous retrovirus particles produced by teratocarcinoma cell lines. J Gen Virol 82(Pt 3):591–596
38. Blume G, Cevc G, Crommelin MD, Bakker-Woudenberg IA, Kluft C, Storm G (1993) Specific targeting with poly(ethylene glycol)-modified liposomes: coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times. Biochim Biophys Acta 1149(1):180–184. doi:10.1016/0005-2736(93)90039-3
39. Boado RJ (2007) Blood–brain barrier transport of non-viral gene and RNAi therapeutics. Pharm Res 24(9):1772–1787. doi:10.1007/s11095-007-9321-5
40. Bobrie A, Colombo M, Raposo G, Thery C (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12(12):1659–1668. doi:10.1111/j.1600-0854.2011.01225.x
41. Boller K, Konig H, Sauter M, Mueller-Lantzsch N, Lower R, Lower J, Kurth R (1993) Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology 196(1):349–353. doi:10.1006/viro.1993.1487
42. Bolukbasi MF, Mizrak A, Ozdener GB, Madlener S, Strobel T, Erkan EP, Fan JB, Breakefield XO, Saydam O (2012) miR-1289 and “Zipcode”-like sequence enrich mRNAs in microvesicles. Mol Ther Nucleic Acids 1:e10. doi:10.1038/mtna.2011.2
43. Bradbury PA, Shepherd FA (2008) Immunotherapy for lung cancer. J Thorac Oncol 3(6 Suppl 2):S164–S170. doi:10.1097/JTO.0b013e318174e9a7
44. Brase JC, Johannes M, Schlomm T, Falth M, Haese A, Steuber T, Beissbarth T, Kuner R, Sultmann H (2011) Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128(3):608–616. doi:10.1002/ijc.25376
45. Bronson DL, Fraley EE, Fogh J, Kalter SS (1979) Induction of retrovirus particles in human testicular tumor (Tera-1) cell cultures: an electron microscopic study. J Natl Cancer Inst 63(2):337–339
46. Brouwers JF, Aalberts M, Jansen JW, van Niel G, Wauben MH, Stout TA, Helms JB, Stoorvogel W (2013) Distinct lipid compositions of two types of human prostasomes. Proteomics 13(10–11):1660–1666. doi:10.1002/pmic.201200348
47. Brown K, Mastrianni JA (2010) The prion diseases. J Geriatr Psychiatry Neurol 23(4):277–298. doi:10.1177/0891988710383576
48. Broz P, Benito SM, Saw C, Burger P, Heider H, Pfisterer M, Marsch S, Meier W, Hunziker P (2005) Cell targeting by a generic receptor-targeted polymer nanocontainer platform. J Control Release 102(2):475–488. doi:10.1016/j.jconrel.2004.10.014
49. Bryant RJ, Pawlowski T, Catto JW, Marsden G, Vessella RL, Rhees B, Kuslich C, Visakorpi T, Hamdy FC (2012) Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 106(4):768–774. doi:10.1038/bjc.2011.595
50. Buyens K, De Smedt SC, Braeckmans K, Demeester J, Peeters L, van Grunsven LA, de Mollerat du Jeu X, Sawant R, Torchilin V, Farkasova K, Ogris M, Sanders NN (2012) Liposome based systems for systemic siRNA delivery: stability in blood sets the requirements for optimal carrier design. J Control Release 158(3):362–370. doi:10.1016/j.jconrel.2011.10.009
51. Camacho L, Guerrero P, Marchetti D (2013) MicroRNA and protein profiling of brain metastasis competent cell-derived exosomes. PLoS One 8(9):e73790. doi:10.1371/journal.pone.0073790
52. Canovi M, Markoutsa E, Lazar AN, Pampalakis G, Clemente C, Re F, Sesana S, Masserini M, Salmona M, Duyckaerts C, Flores O, Gobbi M, Antimisiaris SG (2011) The binding affinity of anti-Abeta1-42 MAb-decorated nanoliposomes to Abeta1-42 peptides in vitro and to amyloid deposits in post-mortem tissue. Biomaterials 32(23):5489–5497. doi:10.1016/j.biomaterials.2011.04.020
53. Cantaluppi V, Gatti S, Medica D, Figliolini F, Bruno S, Deregibus MC, Sordi A, Biancone L, Tetta C, Camussi G (2012) Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells. Kidney Int 82(4):412–427. doi:10.1038/ki.2012.105
54. Cao Z, Tong R, Mishra A, Xu W, Wong GC, Cheng J, Lu Y (2009) Reversible cell-specific drug delivery with aptamer-functionalized liposomes. Angew Chem Int Ed 48(35):6494–6498. doi:10.1002/anie.200901452
55. Carayon K, Chaoui K, Ronzier E, Lazar I, Bertrand-Michel J, Roques V, Balor S, Terce F, Lopez A, Salomé L, Joly E (2011) Proteolipidic composition of exosomes changes during reticulocyte maturation. J Biol Chem 286(39):34426–34439
56. Ceruti S, Colombo L, Magni G, Vigano F, Boccazzi M, Deli MA, Sperlagh B, Abbracchio MP, Kittel A (2011) Oxygen–glucose deprivation increases the enzymatic activity and the microvesicle-mediated release of ectonucleotidases in the cells composing the blood–brain barrier. Neurochem Int 59(2):259–271. doi:10.1016/j.neuint.2011.05.013
57. Chandrawati R, Caruso F (2012) Biomimetic liposome- and polymersome-based multicompartmentalized assemblies. Langmuir 28(39):13798–13807. doi:10.1021/la301958v
58. Chiang WH, Huang WC, Chang CW, Shen MY, Shih ZF, Huang YF, Lin SC, Chiu HC (2013) Functionalized polymersomes with outlayered polyelectrolyte gels for potential tumor-targeted delivery of multimodal therapies and MR imaging. J Control Release 168(3):280–288. doi:10.1016/j.jconrel.2013.03.029
59. Chironi GN, Boulanger CM, Simon A, Dignat-George F, Freyssinet JM, Tedgui A (2009) Endothelial microparticles in diseases. Cell Tissue Res 335(1):143–151. doi:10.1007/s00441-008-0710-9
60. Choi CH, Hao L, Narayan SP, Auyeung E, Mirkin CA (2013) Mechanism for the endocytosis of spherical nucleic acid nanoparticle conjugates. Proc Natl Acad Sci USA 110(19):7625–7630. doi:10.1073/pnas.1305804110
61. Christian DA, Cai S, Bowen DM, Kim Y, Pajerowski JD, Discher DE (2009) Polymersome carriers: from self-assembly to siRNA and protein therapeutics. Eur J Pharm Biopharm 71(3):463–474. doi:10.1016/j.ejpb.2008.09.025
62. Christianson HC, Svensson KJ, van Kuppevelt TH, Li JP, Belting M (2013) Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA 110(43):17380–17385. doi:10.1073/pnas.1304266110
63. Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z (2005) Induction of heat shock proteins in B-cell exosomes. J Cell Sci 118(Pt 16):3631–3638. doi:10.1242/jcs.02494
64. Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z (2007) Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res 67(15):7458–7466. doi:10.1158/0008-5472.CAN-06-3456
65. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19(2):43–51. doi:10.1016/j.tcb.2008.11.003
66. Cogswell JP, Ward J, Taylor IA, Waters M, Shi YL, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, Prinjha RK, Richardson JC, Saunders AM, Roses AD, Richards CA (2008) Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14(1):27–41
67. Coleman BM, Hanssen E, Lawson VA, Hill AF (2012) Prion-infected cells regulate the release of exosomes with distinct ultrastructural features. FASEB J 26(10):4160–4173. doi:10.1096/fj.11-202077
68. Collet G, Grillon C, Nadim M, Kieda C (2013) Trojan horse at cellular level for tumor gene therapies. Gene 525(2):208–216. doi:10.1016/j.gene.2013.03.057
69. Cossetti C, Smith JA, Iraci N, Leonardi T, Alfaro-Cervello C, Pluchino S (2012) Extracellular membrane vesicles and immune regulation in the brain. Front Physiol 3:117. doi:10.3389/fphys.2012.00117
70. Cutler JI, Auyeung E, Mirkin CA (2012) Spherical nucleic acids. J Am Chem Soc 134(3):1376–1391. doi:10.1021/ja209351u
71. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Preat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161(2):505–522. doi:10.1016/j.jconrel.2012.01.043
72. Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, Vanderburg CR, McLean PJ (2012) Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 7:42. doi:10.1186/1750-1326-7-42
73. Das M, Wang C, Bedi R, Mohapatra SS, Mohapatra S (2014) Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury. Nanomedicine. doi:10.1016/j.nano.2014.01.003
74. de Jong OG, Verhaar MC (2012) Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J Extracell Vesicles 1:18396. doi:10.3402/jev.v1i0.18396
75. Del Conde I, Shrimpton CN, Thiagarajan P, Lopez JA (2005) Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106(5):1604–1611. doi:10.1182/blood-2004-03-1095
76. Deng C, Jiang Y, Cheng R, Meng F, Zhong Z (2012) Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: promises, progress and prospects. Nano Today 7(5):467–480. doi:10.1016/j.nantod.2012.08.005
77. Depil S, Roche C, Dussart P, Prin L (2002) Expression of a human endogenous retrovirus, HERV-K, in the blood cells of leukemia patients. Leukemia 16(2):254–259. doi:10.1038/sj.leu.2402355
78. DePinho RA (2000) The age of cancer. Nature 408(6809):248–254. doi:10.1038/35041694
79. Deregibus MC, Cantaluppi V, Calogero R, Lo Iacono M, Tetta C, Biancone L, Bruno S, Bussolati B, Camussi G (2007) Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110(7):2440–2448. doi:10.1182/blood-2007-03-078709
80. Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ (2009) Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA 106(31):13010–13015. doi:10.1073/pnas.0903691106
81. Devadasu VR, Bhardwaj V, Kumar MN (2013) Can controversial nanotechnology promise drug delivery? Chem Rev 113(3):1686–1735. doi:10.1021/cr300047q
82. Dewannieux M, Blaise S, Heidmann T (2005) Identification of a functional envelope protein from the HERV-K family of human endogenous retroviruses. J Virol 79(24):15573–15577. doi:10.1128/JVI.79.24.15573-15577.2005
83. Di Stefano A, Sozio P, Iannitelli A, Marianecci C, Santucci E, Carafa M (2006) Maleic- and fumaric-diamides of (O,O-diacetyl)-l-dopa-methylester as anti-Parkinson prodrugs in liposomal formulation. J Drug Target 14(9):652–661. doi:10.1080/10611860600916636
84. Dihanich S, Manzoni C (2011) LRRK2: a problem lurking in vesicle trafficking? J Neurosci 31(27):9787–9788. doi:10.1523/JNEUROSCI.1976-11.2011
85. Dinkins MB, Dasgupta S, Wang G, Zhu G, Bieberich E (2014) Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol Aging 35(8):1792–1800. doi:10.1016/j.neurobiolaging.2014.02.012
86. Drummond DC, Noble CO, Guo Z, Hong K, Park JW, Kirpotin DB (2006) Development of a highly active nanoliposomal irinotecan using a novel intraliposomal stabilization strategy. Cancer Res 66(6):3271–3277. doi:10.1158/0008-5472.CAN-05-4007
87. Duncan R, Gaspar R (2011) Nanomedicine(s) under the microscope. Mol Pharm 8(6):2101–2141. doi:10.1021/mp200394t
88. El Kazzouli S, Mignani S, Bousmina M, Majoral J-P (2012) Dendrimer therapeutics: covalent and ionic attachments. New J Chem 36(2):227. doi:10.1039/c1nj20459a
89. El-Andaloussi S, Lee Y, Lakhal-Littleton S, Li J, Seow Y, Gardiner C, Alvarez-Erviti L, Sargent IL, Wood MJ (2012) Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc 7(12):2112–2126. doi:10.1038/nprot.2012.131
90. El-Andaloussi S, Mager I, Breakefield XO, Wood MJ (2013) Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 12(5):347–357. doi:10.1038/nrd3978
91. Eldh M, Ekström K, Valadi H, Sjöstrand M, Olsson B (2010) Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA. PLoS One 5(12):e15353. doi:10.1371/journal.pone.0015353
92. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, Stefanis L, Vekrellis K (2010) Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 30(20):6838–6851. doi:10.1523/JNEUROSCI.5699-09.2010
93. Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273(32):20121–20127
94. Esfand R, Tomalia DA (2001) Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 6(8):427–436
95. Fantini M, Gianni L, Santelmo C, Drudi F, Castellani C, Affatato A, Nicolini M, Ravaioli A (2011) Lipoplatin treatment in lung and breast cancer. Chemother Res Pract 2011:125192. doi:10.1155/2011/125192
96. Fasol U, Frost A, Buchert M, Arends J, Fiedler U, Scharr D, Scheuenpflug J, Mross K (2012) Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis. Ann Oncol 23(4):1030–1036. doi:10.1093/annonc/mdr300
97. Faure J, Lachenal G, Court M, Hirrlinger J, Chatellard-Causse C, Blot B, Grange J, Schoehn G, Goldberg Y, Boyer V, Kirchhoff F, Raposo G, Garin J, Sadoul R (2006) Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 31(4):642–648. doi:10.1016/j.mcn.2005.12.003
98. Feng Z (2010) p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment. Cold Spring Harb Perspect Biol 2(2):a001057. doi:10.1101/cshperspect.a001057
99. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G (2004) Cells release prions in association with exosomes. Proc Natl Acad Sci USA 101(26):9683–9688. doi:10.1073/pnas.0308413101
100. Fitzner D, Schnaars M, van Rossum D (2011) Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 124(3):447–458
101. Fruhbeis C, Frohlich D, Kuo WP, Amphornrat J, Thilemann S, Saab AS, Kirchhoff F, Mobius W, Goebbels S, Nave KA, Schneider A, Simons M, Klugmann M, Trotter J, Kramer-Albers EM (2013a) Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol 11(7):e1001604. doi:10.1371/journal.pbio.1001604
102. Fruhbeis C, Frohlich D, Kuo WP, Kramer-Albers EM (2013b) Extracellular vesicles as mediators of neuron-glia communication. Front Cell Neurosci 7:182. doi:10.3389/fncel.2013.00182
103. Gabizon A, Catane R, Uziely B, Kaufman B, Safra T, Cohen R, Martin F, Huang A, Barenholz Y (1994) Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 54(4):987–992
104. Gabriel K, Ingram A, Austin R, Kapoor A, Tang D, Majeed F, Qureshi T, Al-Nedawi K (2013) Regulation of the tumor suppressor PTEN through exosomes: a diagnostic potential for prostate cancer. PLoS One 8(7):e70047. doi:10.1371/journal.pone.0070047
105. Ganta S, Devalapally H, Shahiwala A, Amiji M (2008) A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release 126(3):187–204. doi:10.1016/j.jconrel.2007.12.017
106. Gao X, Wu B, Zhang Q, Chen J, Zhu J, Zhang W, Rong Z, Chen H, Jiang X (2007) Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release 121(3):156–167. doi:10.1016/j.jconrel.2007.05.026
107. Gao H, Pang Z, Jiang X (2013) Targeted delivery of nano-therapeutics for major disorders of the central nervous system. Pharm Res 30(10):2485–2498. doi:10.1007/s11095-013-1122-4
108. Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65(12):5238–5247
109. Ge J, Neofytou E, Lei J, Beygui RE, Zare RN (2012) Protein–polymer hybrid nanoparticles for drug delivery. Small 8(23):3573–3578. doi:10.1002/smll.201200889
110. Gildea JJ, Carlson JM, Schoeffel CD, Carey RM, Felder RA (2013) Urinary exosome miRNome analysis and its applications to salt sensitivity of blood pressure. Clin Biochem 46(12):1131–1134. doi:10.1016/j.clinbiochem.2013.05.052
111. Gladnikoff M, Shimoni E, Gov NS, Rousso I (2009) Retroviral assembly and budding occur through an actin-driven mechanism. Biophys J 97(9):2419–2428. doi:10.1016/j.bpj.2009.08.016
112. Gobbi M, Re F, Canovi M, Beeg M, Gregori M, Sesana S, Sonnino S, Brogioli D, Musicanti C, Gasco P, Salmona M, Masserini ME (2010) Lipid-based nanoparticles with high binding affinity for amyloid-beta1-42 peptide. Biomaterials 31(25):6519–6529. doi:10.1016/j.biomaterials.2010.04.044
113. Golan M, Hizi A, Resau JH, Yaal-Hahoshen N, Reichman H, Keydar I, Tsarfaty I (2008) Human endogenous retrovirus (HERV-K) reverse transcriptase as a breast cancer prognostic marker. Neoplasia 10(6):521–533. doi:10.1593/neo.07986
114. Gould SJ, Raposo G (2013) As we wait: coping with an imperfect nomenclature for extracellular vesicles. J Extracell Vesicles 2. doi:10.3402/jev.v2i0.20389
115. Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, Tetta C, Bussolati B, Camussi G (2011) Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res 71(15):5346–5356. doi:10.1158/0008-5472.CAN-11-0241
116. Gregoriadis G, Ryman BE (1971) Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases. Biochem J 124(5):58P
117. Gross JC, Chaudhary V, Bartscherer K, Boutros M (2012) Active Wnt proteins are secreted on exosomes. Nat Cell Biol 14(10):1036–1045. doi:10.1038/ncb2574
118. Guescini M, Genedani S, Stocchi V, Agnati LF (2010) Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J Neural Transm 117(1):1–4. doi:10.1007/s00702-009-0288-8
119. Guo P (2010) The emerging field of RNA nanotechnology. Nat Nanotechnol 5(12):833–842. doi:10.1038/nnano.2010.231
120. Gupta S, Knowlton AA (2007) HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol 292(6):H3052–H3056. doi:10.1152/ajpheart.01355.2006
121. Hajrasouliha AR, Jiang G, Lu Q, Lu H, Kaplan HJ, Zhang HG, Shao H (2013) Exosomes from retinal astrocytes contain antiangiogenic components that inhibit laser-induced choroidal neovascularization. J Biol Chem 288(39):28058–28067. doi:10.1074/jbc.M113.470765
122. Halliday GM, Stevens CH (2011) Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 26(1):6–17. doi:10.1002/mds.23455
123. Haney MJ, Zhao Y, Li S, Higginbotham SM, Booth SL, Han HY, Vetro JA, Mosley RL, Kabanov AV, Gendelman HE, Batrakova EV (2011) Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells. Nanomedicine 6(7):1215–1230. doi:10.2217/nnm.11.32
124. Hansen C, Angot E, Bergstrom AL, Steiner JA, Pieri L, Paul G, Outeiro TF, Melki R, Kallunki P, Fog K, Li JY, Brundin P (2011) Alpha-synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest 121(2):715–725. doi:10.1172/JCI43366
125. Haque F, Shu D, Shu Y, Shlyakhtenko LS, Rychahou PG, Evers BM, Guo P (2012) Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers. Nano Today 7(4):245–257. doi:10.1016/j.nantod.2012.06.010
126. Hawari FI, Rouhani FN, Cui X, Yu ZX, Buckley C, Kaler M, Levine SJ (2004) Release of full-length 55-kDa TNF receptor 1 in exosome-like vesicles: a mechanism for generation of soluble cytokine receptors. Proc Natl Acad Sci USA 101(5):1297–1302. doi:10.1073/pnas.0307981100
127. Hedlund M, Stenqvist A-C, Nagaeva O, Kjellberg L, Wulff M, Baranov V, Mincheva-Nilsson L (2009) Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: evidence for immunosuppressive function. J Immunol 183(1):340–351. doi:10.4049/jimmunol.0803477
128. Heegaard PM, Boas U, Otzen DE (2007) Dendrimer effects on peptide and protein fibrillation. Macromol Biosci 7(8):1047–1059. doi:10.1002/mabi.200700051
129. Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ (1999) Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94(11):3791–3799
130. Hemler ME (2003) Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 19:397–422. doi:10.1146/annurev.cellbio.19.111301.153609
131. Hendriks BS, Klinz SG, Reynolds JG, Espelin CW, Gaddy DF, Wickham TJ (2013) Impact of tumor HER2/ERBB2 expression level on HER2-targeted liposomal doxorubicin-mediated drug delivery: multiple low-affinity interactions lead to a threshold effect. Mol Cancer Ther 12(9):1816–1828. doi:10.1158/1535-7163.MCT-13-0180
132. Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14(3):249–256. doi:10.1038/ncb2441
133. Hessvik NP, Sandvig K, Llorente A (2013) Exosomal miRNAs as biomarkers for prostate cancer. Front Genet 4:36. doi:10.3389/fgene.2013.00036
134. Hickman DT, Lopez-Deber MP, Ndao DM, Silva AB, Nand D, Pihlgren M, Giriens V, Madani R, St-Pierre A, Karastaneva H, Nagel-Steger L, Willbold D, Riesner D, Nicolau C, Baldus M, Pfeifer A, Muhs A (2011) Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases. J Biol Chem 286(16):13966–13976. doi:10.1074/jbc.M110.186338
135. Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S, Lauterbach MA, Bakhti M, Gronborg M, Mobius W, Rhee J, Barr FA, Simons M (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189(2):223–232. doi:10.1083/jcb.200911018
136. Hu K, Li J, Shen Y, Lu W, Gao X, Zhang Q, Jiang X (2009) Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations. J Control Release 134(1):55–61. doi:10.1016/j.jconrel.2008.10.016
137. Hu K, Shi Y, Jiang W, Han J, Huang S, Jiang X (2011) Lactoferrin conjugated PEG–PLGA nanoparticles for brain delivery: preparation, characterization and efficacy in Parkinson’s disease. Int J Pharm 415(1–2):273–283. doi:10.1016/j.ijpharm.2011.05.062
138. Hu G, Yao H, Chaudhuri AD, Duan M, Yelamanchili SV, Wen H, Cheney PD, Fox HS, Buch S (2012) Exosome-mediated shuttling of microRNA-29 regulates HIV Tat and morphine-mediated Neuronal dysfunction. Cell Death Dis 3:e381. doi:10.1038/cddis.2012.114
139. Huber V, Fais S, Iero M, Lugini L, Canese P, Squarcina P, Zaccheddu A, Colone M, Arancia G, Gentile M, Seregni E, Valenti R, Ballabio G, Belli F, Leo E, Parmiani G, Rivoltini L (2005) Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape. Gastroenterology 128(7):1796–1804. doi:10.1053/j.gastro.2005.03.045
140. Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM (2005) Membrane microparticles: two sides of the coin. Physiology 20:22–27. doi:10.1152/physiol.00029.2004
141. Hung CW, Chen YC, Hsieh WL, Chiou SH, Kao CL (2010) Ageing and neurodegenerative diseases. Ageing Res Rev 9(Suppl 1):S36–S46. doi:10.1016/j.arr.2010.08.006
142. Huttner HB, Janich P, Kohrmann M, Jaszai J, Siebzehnrubl F, Blumcke I, Suttorp M, Gahr M, Kuhnt D, Nimsky C, Krex D, Schackert G, Lowenbruck K, Reichmann H, Juttler E, Hacke W, Schellinger PD, Schwab S, Wilsch-Brauninger M, Marzesco AM, Corbeil D (2008) The stem cell marker prominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease. Stem Cells 26(3):698–705. doi:10.1634/stemcells.2007-0639
143. Iero M, Valenti R, Huber V, Filipazzi P, Parmiani G, Fais S, Rivoltini L (2007) Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15(1):80–88. doi:10.1038/sj.cdd.4402237
144. Jang SC, Kim OY, Yoon CM, Choi DS, Roh TY, Park J, Nilsson J, Lotvall J, Kim YK, Gho YS (2013) Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 7(9):7698–7710. doi:10.1021/nn402232g
145. Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113(5):752–760. doi:10.1002/ijc.20657
146. Jayaraman M, Ansell SM, Mui BL, Tam YK, Chen J, Du X, Butler D, Eltepu L, Matsuda S, Narayanannair JK, Rajeev KG, Hafez IM, Akinc A, Maier MA, Tracy MA, Cullis PR, Madden TD, Manoharan M, Hope MJ (2012) Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew Chem Int Ed 51(34):8529–8533. doi:10.1002/anie.201203263
147. Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP, Kouri FM, Merkel TJ, Luthi AJ, Patel PC, Cutler JI, Daniel WL, Scott AW, Rotz MW, Meade TJ, Giljohann DA, Mirkin CA, Stegh AH (2013) Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Transl Med 5(209):209RA152. doi:10.1126/scitranslmed.3006839
148. Jeong JH, Park TG, Kim SH (2011) Self-assembled and nanostructured siRNA delivery systems. Pharm Res 28(9):2072–2085. doi:10.1007/s11095-011-0412-y
149. Jo W, Jeong D, Kim J, Cho S, Jang SC, Han C, Kang JY, Gho YS, Park J (2014) Microfluidic fabrication of cell-derived nanovesicles as endogenous RNA carriers. Lab Chip 14(7):1261–1269. doi:10.1039/c3lc50993a
150. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262(19):9412–9420
151. Joshi P, Turola E, Ruiz A, Bergami A, Libera DD, Benussi L, Giussani P, Magnani G, Comi G, Legname G, Ghidoni R, Furlan R, Matteoli M, Verderio C (2014) Microglia convert aggregated amyloid-beta into neurotoxic forms through the shedding of microvesicles. Cell Death Differ 21(4):582–593. doi:10.1038/cdd.2013.180
152. Jung KH, Chu K, Lee ST, Park HK, Bahn JJ, Kim DH, Kim JH, Kim M, Kun Lee S, Roh JK (2009) Circulating endothelial microparticles as a marker of cerebrovascular disease. Ann Neurol 66(2):191–199. doi:10.1002/ana.21681
153. Jy W, Minagar A, Jimenez JJ, Sheremata WA, Mauro LM, Horstman LL, Bidot C, Ahn YS (2004) Endothelial microparticles (EMP) bind and activate monocytes: elevated EMP-monocyte conjugates in multiple sclerosis. Front Biosci 9:3137–3144. doi:10.2741/1466
154. Kalani A, Tyagi A, Tyagi N (2013) Exosomes: mediators of neurodegeneration, neuroprotection and therapeutics. Mol Neurobiol 49(1):590–600. doi:10.1007/s12035-013-8544-1
155. Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, Bond VC, Borràs FE, Breakefield X, Budnik V, Buzas E, Camussi G, Clayton A, Cocucci E, Falcon-Perez JM, Gabrielsson S, Gho YS, Gupta D, Harsha HC, Hendrix A, Hill AF, Inal JM, Jenster G, Krämer-Albers E-M, Lim SK, Llorente A, Lotvall J, Marcilla A, Mincheva-Nilsson L, Nazarenko I, Nieuwland R, Nolte-’t Hoen ENM, Pandey A, Patel T, Piper MG, Pluchino S, Prasad TSK, Rajendran L, Raposo G, Record M, Reid GE, Sánchez-Madrid F, Schiffelers RM, Siljander P, Stensballe A, Stoorvogel W, Taylor D, Théry C, Valadi H, van Balkom BWM, Vázquez J, Vidal M, Wauben MHM, Yáñez-Mó M, Zoeller M, Mathivanan S (2012) Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol 10(12):e1001450
156. Kanasty R, Dorkin JR, Vegas A, Anderson D (2013) Delivery materials for siRNA therapeutics. Nat Mater 12(11):967–977. doi:10.1038/nmat3765
157. Kanazawa T, Akiyama F, Kakizaki S, Takashima Y, Seta Y (2013) Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles. Biomaterials 34(36):9220–9226. doi:10.1016/j.biomaterials.2013.08.036
158. Karolina DS, Tavintharan S, Armugam A, Sepramaniam S, Pek SLT, Wong MTK, Lim SC, Sum CF, Jeyaseelan K (2012) Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab 97(12):E2271–E2276. doi:10.1210/jc.2012-1996
159. Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M (2013) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335(1):201–204. doi:10.1016/j.canlet.2013.02.019
160. Kesharwani P, Jain K, Jain NK (2014) Dendrimer as nanocarrier for drug delivery. Prog Polym Sci 39(2):268–307. doi:10.1016/j.progpolymsci.2013.07.005
161. Keum JW, Ahn JH, Bermudez H (2011) Design, assembly, and activity of antisense DNA nanostructures. Small 7(24):3529–3535. doi:10.1002/smll.201101804
162. Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, Kim NK, Bang YJ (2004) Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res 10(11):3708–3716. doi:10.1158/1078-0432.CCR-03-0655
163. Knupfer MM, Poppenborg H, Hotfilder M, Kuhnel K, Wolff JE, Domula M (1999) CD44 expression and hyaluronic acid binding of malignant glioma cells. Clin Exp Metastasis 17(1):71–76. doi:10.1023/A:1026425519497
164. Kobayashi M, Salomon C, Tapia J, Illanes SE, Mitchell MD, Rice GE (2014) Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200. J Transl Med 12:12. doi:10.1186/1479-5876-12-4
165. Kogure T, Lin W-L, Yan IK, Braconi C, Patel T (2011) Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 54(4):1237–1248. doi:10.1002/hep.24504
166. Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM (2012) Exosome mimetics: a novel class of drug delivery systems. Int J Nanomed 7:1525–1541. doi:10.2147/IJN.S29661
167. Kooijmans SA, Stremersch S, Braeckmans K, de Smedt SC, Hendrix A, Wood MJ, Schiffelers RM, Raemdonck K, Vader P (2013) Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J Control Release 172(1):229–238. doi:10.1016/j.jconrel.2013.08.014
168. Koppers-Lalic D, Hogenboom MM, Middeldorp JM, Pegtel DM (2013) Virus-modified exosomes for targeted RNA delivery; a new approach in nanomedicine. Adv Drug Deliv Rev 65(3):348–356. doi:10.1016/j.addr.2012.07.006
169. Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, Budnik V (2009) Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 139(2):393–404. doi:10.1016/j.cell.2009.07.051
170. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285(23):17442–17452. doi:10.1074/jbc.M110.107821
171. Kosaka N, Iguchi H, Yoshioka Y, Hagiwara K, Takeshita F, Ochiya T (2012) Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem 287(2):1397–1405. doi:10.1074/jbc.M111.288662
172. Kosaka N, Takeshita F, Yoshioka Y, Hagiwara K, Katsuda T, Ono M, Ochiya T (2013) Exosomal tumor-suppressive microRNAs as novel cancer therapy: “exocure” is another choice for cancer treatment. Adv Drug Deliv Rev 65(3):376–382. doi:10.1016/j.addr.2012.07.011
173. Kovacs GG, Budka H (2002) Aging, the brain and human prion disease. Exp Gerontol 37(4):603–605. doi:10.1016/S0531-5565(01)00219-4
174. Kramer-Albers EM, Bretz N, Tenzer S, Winterstein C, Mobius W, Berger H, Nave KA, Schild H, Trotter J (2007) Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteomics Clin Appl 1(11):1446–1461. doi:10.1002/prca.200700522
175. Krtolica A, Campisi J (2002) Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol 34(11):1401–1414. doi:10.1016/S1357-2725(02)00053-5
176. Kruger S, Abd Elmageed ZY, Hawke DH, Woerner PM, Jansen DA, Abdel-Mageed AB, Alt EU, Izadpanah R (2014) Molecular characterization of exosome-like vesicles from breast cancer cells. BMC Cancer 14:14. doi:10.1186/1471-2407-14-44
177. Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E, Ringner M, Morgelin M, Bourseau-Guilmain E, Bengzon J, Belting M (2013) Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci USA 110(18):7312–7317. doi:10.1073/pnas.1220998110
178. Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T (2011) Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet 4(4):446–454. doi:10.1161/circgenetics.110.958975
179. Lachenal G, Pernet-Gallay K, Chivet M, Hemming FJ, Belly A, Bodon G, Blot B, Haase G, Goldberg Y, Sadoul R (2011) Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol Cell Neurosci 46(2):409–418. doi:10.1016/j.mcn.2010.11.004
180. Lai CP, Breakefield XO (2012) Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Front Physiol 3:228. doi:10.3389/fphys.2012.00228
181. Lai RC, Yeo RW, Tan KH, Lim SK (2013) Exosomes for drug delivery—a novel application for the mesenchymal stem cell. Biotechnol Adv 31(5):543–551. doi:10.1016/j.biotechadv.2012.08.008
182. Lakhal S, Wood MJ (2011) Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers. BioEssays 33(10):737–741. doi:10.1002/bies.201100076
183. Lancaster GI, Febbraio MA (2005) Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem 280(24):23349–23355
184. Lao J, Madani J, Puertolas T, Alvarez M, Hernandez A, Pazo-Cid R, Artal A, Anton Torres A (2013) Liposomal doxorubicin in the treatment of breast cancer patients: a review. J Drug Deliv 2013:456409. doi:10.1155/2013/456409
185. Lau C, Kim Y, Chia D, Spielmann N, Eibl G, Elashoff D, Wei F, Lin YL, Moro A, Grogan T, Chiang S, Feinstein E, Schafer C, Farrell J, Wong DT (2013) Role of pancreatic cancer-derived exosomes in salivary biomarker development. J Biol Chem 288(37):26888–26897. doi:10.1074/jbc.M113.452458
186. Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F, Pageaux JF, Kobayashi T, Salles JP, Perret B, Bonnerot C, Record M (2004) Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 380(Pt 1):161–171. doi:10.1042/BJ20031594
187. Lee JS, Feijen J (2012) Polymersomes for drug delivery: design, formation and characterization. J Control Release 161(2):473–483. doi:10.1016/j.jconrel.2011.10.005
188. Lee RJ, Low PS (1994) Delivery of liposomes into cultured Kb cells via folate receptor-mediated endocytosis. J Biol Chem 269(5):3198–3204
189. Lee TW, Matthews DA, Blair GE (2005) Novel molecular approaches to cystic fibrosis gene therapy. Biochem J 387(Pt 1):1–15. doi:10.1042/BJ20041923
190. Lee HJ, Suk JE, Bae EJ, Lee JH, Paik SR, Lee SJ (2008) Assembly-dependent endocytosis and clearance of extracellular alpha-synuclein. Int J Biochem Cell Biol 40(9):1835–1849. doi:10.1016/j.biocel.2008.01.017
191. Lee HJ, Suk JE, Patrick C, Bae EJ, Cho JH, Rho S, Hwang D, Masliah E, Lee SJ (2010) Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 285(12):9262–9272. doi:10.1074/jbc.M109.081125
192. Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J (2011) Microvesicles as mediators of intercellular communication in cancer–the emerging science of cellular ‘debris’. Semin Immunopathol 33(5):455–467. doi:10.1007/s00281-011-0250-3
193. Lee H, Lytton-Jean AK, Chen Y, Love KT, Park AI, Karagiannis ED, Sehgal A, Querbes W, Zurenko CS, Jayaraman M, Peng CG, Charisse K, Borodovsky A, Manoharan M, Donahoe JS, Truelove J, Nahrendorf M, Langer R, Anderson DG (2012a) Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat Nanotechnol 7(6):389–393. doi:10.1038/nnano.2012.73
194. Lee JB, Hong J, Bonner DK, Poon Z, Hammond PT (2012b) Self-assembled RNA interference microsponges for efficient siRNA delivery. Nat Mater 11(4):316–322. doi:10.1038/nmat3253
195. Lee J-K, Park S-R, Jung B-K, Jeon Y-K, Lee Y-S, Kim M-K, Kim Y-G, Jang J-Y, Kim C-W (2013) Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS ONE 8(12):e84256. doi:10.1371/journal.pone.0084256
196. Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373(9680):2055–2066. doi:10.1016/S0140-6736(09)60492-X
197. Lespagnol A, Duflaut D, Beekman C, Blanc L, Fiucci G, Marine JC, Vidal M, Amson R, Telerman A (2008) Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death Differ 15(11):1723–1733. doi:10.1038/cdd.2008.104
198. Levanen B, Bhakta NR, Paredes PT, Barbeau R, Hiltbrunner S, Pollack JL, Skold CM, Svartengren M, Grunewald J, Gabrielsson S, Eklund A, Larsson BM, Woodruff PG, Erle DJ, Wheelock AM (2013) Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients. J Allergy Clin Immunol 131(3):894–903. doi:10.1016/j.jaci.2012.11.039
199. Leventis PA, Grinstein S (2010) The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys 39:407–427. doi:10.1146/annurev.biophys.093008.131234
200. Levesque K, Halvorsen M, Abrahamyan L, Chatel-Chaix L, Poupon V, Gordon H, DesGroseillers L, Gatignol A, Mouland AJ (2006) Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein A2 expression and impacts on viral assembly. Traffic 7(9):1177–1193. doi:10.1111/j.1600-0854.2006.00461.x
201. Levine DH, Ghoroghchian PP, Freudenberg J, Zhang G, Therien MJ, Greene MI, Hammer DA, Murali R (2008) Polymersomes: a new multi-functional tool for cancer diagnosis and therapy. Methods 46(1):25–32. doi:10.1016/j.ymeth.2008.05.006
202. Li J, Liu K, Liu Y, Xu Y, Zhang F, Yang H, Liu J, Pan T, Chen J, Wu M, Zhou X, Yuan Z (2013a) Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity. Nat Immunol 14:793–803. doi:10.1038/ni.2647
203. Li J, Zhang C, Li J, Fan L, Jiang X, Chen J, Pang Z, Zhang Q (2013b) Brain delivery of NAP with PEG-PLGA nanoparticles modified with phage display peptides. Pharm Res 30(7):1813–1823. doi:10.1007/s11095-013-1025-4
204. Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y, Kappes JC, Barnes S, Kimberly RP, Grizzle WE, Zhang HG (2006) Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol 176(3):1375–1385
205. Liu X-Q, Sun CY, Yang XZ, Wang J (2013) Polymeric-micelle-based nanomedicine for siRNA delivery. Part Part Syst Charact 30(3):211–228. doi:10.1002/ppsc.201200061
206. Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B (2009) Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One 4(7):e6229. doi:10.1371/journal.pone.0006229
207. Lopez-Verrilli MA, Court FA (2012) Transfer of vesicles from Schwann cells to axons: a novel mechanism of communication in the peripheral nervous system. Front Physiol 3:205. doi:10.3389/fphys.2012.00205
208. Lopez-Verrilli MA, Picou F, Court FA (2013) Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 61(11):1795–1806. doi:10.1002/glia.22558
209. LoPresti C, Lomas H, Massignani M, Smart T, Battaglia G (2009) Polymersomes: nature inspired nanometer sized compartments. J Mater Chem 19(22):3576–3590. doi:10.1039/B818869f
210. Lv LL, Cao YH, Ni HF, Xu M, Liu D, Liu H, Chen PS, Liu BC (2013) MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. Am J Physiol-Renal Physiol 305(8):F1220–F1227. doi:10.1152/ajprenal.00148.2013
211. Mack M, Kleinschmidt A, Bruhl H, Klier C, Nelson PJ, Cihak J, Plachy J, Stangassinger M, Erfle V, Schlondorff D (2000) Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med 6(7):769–775. doi:10.1038/77498
212. Malmsten M (2013) Inorganic nanomaterials as delivery systems for proteins, peptides, DNA, and siRNA. Curr Opin Colloid Int Sci 18(5):468–480. doi:10.1016/j.cocis.2013.06.002
213. Mangeot PE, Dollet S, Girard M, Ciancia C, Joly S, Peschanski M, Lotteau V (2011) Protein transfer into human cells by VSV-G-induced nanovesicles. Mol Ther 19(9):1656–1666. doi:10.1038/mt.2011.138
214. Martinez MC, Freyssinet JM (2001) Deciphering the plasma membrane hallmarks of apoptotic cells: phosphatidylserine transverse redistribution and calcium entry. BMC Cell Biol 2:20. doi:10.1186/1471-2121-2-20
215. Martinez-Fong D, Bannon MJ, Trudeau LE, Gonzalez-Barrios JA, Arango-Rodriguez ML, Hernandez-Chan NG, Reyes-Corona D, Armendariz-Borunda J, Navarro-Quiroga I (2012) NTS-Polyplex: a potential nanocarrier for neurotrophic therapy of Parkinson’s disease. Nanomedicine 8(7):1052–1069. doi:10.1016/j.nano.2012.02.009
216. Marzesco AM, Janich P, Wilsch-Brauninger M, Dubreuil V, Langenfeld K, Corbeil D, Huttner WB (2005) Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci 118(Pt 13):2849–2858. doi:10.1242/jcs.02439
217. Meckes DG Jr, Shair KHY, Marquitz AR, Kung CP, Edwards RH, Raab-Traub N (2010) Human tumor virus utilizes exosomes for intercellular communication. Proc Natl Acad Sci USA 107(47):20370–20375. doi:10.1073/pnas.1014194107
218. McConnell RE, Higginbotham JN, Shifrin DA Jr, Tabb DL, Coffey RJ, Tyska MJ (2009) The enterocyte microvillus is a vesicle-generating organelle. J Cell Biol 185(7):1285–1298. doi:10.1083/jcb.200902147
219. Michael A, Bajracharya SD, Yuen PST, Zhou H, Star RA, Illei GG, Alevizos I (2010) Exosomes from human saliva as a source of microRNA biomarkers. Oral Diseases 16(1):34–38. doi:10.1111/j.1601-0825.2009.01604.x
220. Mills JC, Stone NL, Erhardt J, Pittman RN (1998) Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation. J Cell Biol 140(3):627–636. doi:10.1083/jcb.140.3.627
221. Minagar A, Jy W, Jimenez JJ, Sheremata WA, Mauro LM, Mao WW, Horstman LL, Ahn YS (2001) Elevated plasma endothelial microparticles in multiple sclerosis. Neurology 56(10):1319–1324
222. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105(30):10513–10518. doi:10.1073/pnas.0804549105
223. Moltzahn F, Olshen AB, Baehner L, Peek A, Fong L, Stoppler H, Simko J, Hilton JF, Carroll P, Blelloch R (2011) Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res 71(2):550–560. doi:10.1158/0008-5472.can-10-1229
224. Montecalvo A, Larregina AT, Shufesky WJ, Beer Stolz D, Sullivan MLG, Karlsson JM, Baty CJ, Gibson GA, Erdos G, Wang Z, Milosevic J, Tkacheva OA, Divito SJ, Jordan R, Lyons-Weiler J, Watkins SC, Morelli AE (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119(3):756–766. doi:10.1182/blood-2011-02-338004
225. Morel O, Morel N, Jesel L, Freyssinet JM, Toti F (2011) Microparticles: a critical component in the nexus between inflammation, immunity, and thrombosis. Semin Immunopathol 33(5):469–486. doi:10.1007/s00281-010-0239-3
226. Morelli AE, Larregina AT, Shufesky WJ (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104(10):3257–3266. doi:10.1182/blood-2004-03-0824
227. Mourtas S, Canovi M, Zona C, Aurilia D, Niarakis A, La Ferla B, Salmona M, Nicotra F, Gobbi M, Antimisiaris SG (2011) Curcumin-decorated nanoliposomes with very high affinity for amyloid-beta1-42 peptide. Biomaterials 32(6):1635–1645. doi:10.1016/j.biomaterials.2010.10.027
228. Mueller G, Schneider M, Biemer-Daub G, Wied S (2011) Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. Cell Signal 23(7):1207–1223. doi:10.1016/j.cellsig.2011.03.013
229. Mueller-Lantzsch N, Sauter M, Weiskircher A, Kramer K, Best B, Buck M, Grasser F (1993) Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. AIDS Res Hum Retroviruses 9(4):343–350. doi:10.1089/aid.1993.9.343
230. Muhs A, Hickman DT, Pihlgren M, Chuard N, Giriens V, Meerschman C, van der Auwera I, van Leuven F, Sugawara M, Weingertner MC, Bechinger B, Greferath R, Kolonko N, Nagel-Steger L, Riesner D, Brady RO, Pfeifer A, Nicolau C (2007) Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc Natl Acad Sci USA 104(23):9810–9815. doi:10.1073/pnas.0703137104
231. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P (2013) Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol Ther Nucleic Acids 2:e126. doi:10.1038/mtna.2013.60
232. Munro TP, Magee RJ, Kidd GJ, Carson JH, Barbarese E, Smith LM, Smith R (1999) Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking. J Biol Chem 274(48):34389–34395
233. Muralidharan-Chari V, Clancy J, Plou C, Romao M, Chavrier P, Raposo G, D’Souza-Schorey C (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885. doi:10.1016/j.cub.2009.09.059
234. Mutlu NB, Degim Z, Yilmaz S, Essiz D, Nacar A (2011) New perspective for the treatment of Alzheimer diseases: liposomal rivastigmine formulations. Drug Dev Ind Pharm 37(7):775–789. doi:10.3109/03639045.2010.541262
235. Nabhan JF, Hu R, Oh RS, Cohen SN, Lu Q (2012) Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc Natl Acad Sci USA 109(11):4146–4151. doi:10.1073/pnas.1200448109
236. Nguyen DG, Booth A, Gould SJ, Hildreth JEK (2003) Evidence that HIV budding in primary macrophages occurs through the exosome release pathway. J Biol Chem 278(52):52347–52354. doi:10.1074/jbc.M309009200
237. Nicolau C, Greferath R, Balaban T, Lazarte J, Hopkins R (2002) A liposome-based therapeutic vaccine against beta-amyloid plaques on the pancreas of transgenic NORBA mice. Proc Natl Acad Sci USA 99(4):2332–2337. doi:10.1073/pnas.022627199
238. Noble GT, Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B (2014) Ligand-targeted liposome design: challenges and fundamental considerations. Trends Biotechnol 32(1):32–45. doi:10.1016/j.tibtech.2013.09.007
239. Nolte-’t Hoen ENM, Buschow SI, Anderton SM, Stoorvogel W, Wauben MHM (2009) Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 113(9):1977–1981. doi:10.1182/blood-2008-08-174094
240. Nolte-’t Hoen EN, van der Vlist EJ, Aalberts M, Mertens HC, Bosch BJ, Bartelink W, Mastrobattista E, van Gaal EV, Stoorvogel W, Arkesteijn GJ, Wauben MH (2012) Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles. Nanomedicine 8(5):712–720. doi:10.1016/j.nano.2011.09.006
241. Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, Gunji T, Ohta H, Okamoto H, Sonoda H, Watanabe M, Nakagama H, Yokota J, Kohno T, Tsuchiya N (2014) Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 9(4):9. doi:10.1371/journal.pone.0092921
242. Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21(1):185–191. doi:10.1038/mt.2012.180
243. Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, Muramatsu K, Fukuda Y, Ogura S, Yamaguchi K, Mochizuki T (2010) Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 5(10):e13247. doi:10.1371/journal.pone.0013247
244. Olson SD, Kambal A, Pollock K, Mitchell GM, Stewart H, Kalomoiris S, Cary W, Nacey C, Pepper K, Nolta JA (2012) Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington’s disease affected neuronal cells for reduction of huntingtin. Mol Cell Neurosci 49(3):271–281. doi:10.1016/j.mcn.2011.12.001
245. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19–30. doi:10.1038/ncb2000 sup pp 11–13
246. Palma J, Yaddanapudi SC, Pigati L, Havens MA, Jeong S, Weiner GA, Weimer KME, Stern B, Hastings ML, Duelli DM (2012) MicroRNAs are exported from malignant cells in customized particles. Nucleic Acids Res 40(18):9125–9138. doi:10.1093/nar/gks656
247. Pang Z, Lu W, Gao H, Hu K, Chen J, Zhang C, Gao X, Jiang X, Zhu C (2008) Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. J Control Release 128(2):120–127. doi:10.1016/j.jconrel.2008.03.007
248. Pang Z, Feng L, Hua R, Chen J, Gao H, Pan S, Jiang X, Zhang P (2010) Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats. Mol Pharm 7(6):1995–2005. doi:10.1021/mp100277h
249. Pang Z, Gao H, Yu Y, Guo L, Chen J, Pan S, Ren J, Wen Z, Jiang X (2011) Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem 22(6):1171–1180. doi:10.1021/bc200062q
250. Pangburn T, Georgiou K, Bates F, Kokkoli E (2012) Targeted polymersome delivery of siRNA induces cell death of breast cancer cells dependent upon Orai3 protein expression. Langmuir 28(35):12816–12830. doi:10.1021/la300874z
251. Park J, Tan H, Datta A, Lai R, Zhang H, Meng W, Lim S, Sze S (2010) Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Prot 9(6):1085–1099. doi:10.1074/mcp.M900381-MCP200
252. Patel DM, Arnold PY, White GA, Nardella JP, Mannie MD (1999) Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J Immunol 163(10):5201–5210
253. Patel DA, Henry JE, Good TA (2007) Attenuation of beta-amyloid-induced toxicity by sialic-acid-conjugated dendrimers: role of sialic acid attachment. Brain Res 1161:95–105. doi:10.1016/j.brainres.2007.05.055
254. Paula-Barbosa M, Mota Cardoso R, Faria R, Cruz C (1978) Multivesicular bodies in cortical dendrites of two patients with Alzheimer’s disease. J Neurol Sci 36(2):259–264. doi:10.1016/0022-510X(78)90086-2
255. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MAJ, Hopmans ES, Lindenberg JL, de Gruijl TD, Wurdinger T, Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA 107(14):6328–6333. doi:10.1073/pnas.0914843107
256. Pelloski CE, Ballman KV, Furth AF, Zhang L, Lin E, Sulman EP, Bhat K, McDonald JM, Yung WK, Colman H, Woo SY, Heimberger AB, Suki D, Prados MD, Chang SM, Barker FG II, Buckner JC, James CD, Aldape K (2007) Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol 25(16):2288–2294. doi:10.1200/jco.2006.08.0705
257. Piccoli G, Condliffe SB, Bauer M, Giesert F, Boldt K, De Astis S, Meixner A, Sarioglu H, Vogt-Weisenhorn DM, Wurst W, Gloeckner CJ, Matteoli M, Sala C, Ueffing M (2011) LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. J Neurosci 31(6):2225–2237. doi:10.1523/JNEUROSCI.3730-10.2011
258. Pincetic A, Leis J (2009) The mechanism of budding of retroviruses from cell membranes. Adv Virol 2009:623969. doi:10.1155/2009/623969
259. Piper RC, Katzmann DJ (2007) Biogenesis and function of multivesicular bodies. Annu Rev Cell Dev Biol 23:519–547. doi:10.1146/annurev.cellbio.23.090506.123319
260. Potolicchio I, Carven GJ, Xu X, Stipp C, Riese RJ, Stern LJ, Santambrogio L (2005) Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol 175(4):2237–2243
261. Pourtau L, Oliveira H, Thevenot J, Wan Y, Brisson A, Sandre O, Miraux S, Thiaudiere E, Lecommandoux S (2013) Antibody-functionalized magnetic polymersomes: in vivo targeting and imaging of bone metastases using high resolution MRI. Adv Healthcare Mater 2(11):1420–1424. doi:10.1002/adhm.201300061
262. Principe S, Hui A, Bruce J, Sinha A, Liu F-F, Kislinger T (2013) Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics 13(10–11):1608–1623. doi:10.1002/pmic.201200533
263. Pusic AD, Kraig RP (2014) Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination. Glia 62(2):284–299. doi:10.1002/glia.22606
264. Pusic AD, Pusic KM, Clayton BL, Kraig RP (2014) IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J Neuroimmunol 266(1–2):12–23. doi:10.1016/j.jneuroim.2013.10.014
265. Putz U, Howitt J, Lackovic J, Foot N, Kumar S, Silke J, Tan SS (2008) Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. J Biol Chem 283(47):32621–32627. doi:10.1074/jbc.M804120200
266. Qu Y, Franchi L, Nunez G, Dubyak GR (2007) Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J Immunol 179(3):1913–1925
267. Querfurth H, LaFerla F (2010) Alzheimer’s disease. N Engl J Med 362:329–344
268. Rai K, Takigawa N, Ito S, Kashihara H, Ichihara E, Yasuda T, Shimizu K, Tanimoto M, Kiura K (2011) Liposomal delivery of microRNA-7-expressing plasmid overcomes epidermal growth factor receptor tyrosine kinase inhibitor-resistance in lung cancer cells. Mol Cancer Ther 10(9):1720–1727. doi:10.1158/1535-7163.MCT-11-0220
269. Rajendra KS, Hae-Won K (2013) Inorganic nanobiomaterial drug carriers for medicine. Tissue Eng Regenerative Med 10(6):296–309. doi:10.1007/s13770-013-1092-y
270. Rajendran L, Honsho M, Zahn T (2006) Alzheimer’s disease β-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci USA 103(30):11172–11177. doi:10.1073/pnas.0603838103
271. Rana S, Malinowska K, Zöller M (2013) Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia 15(3):281–295. doi:10.1593/neo.122010
272. Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383. doi:10.1083/jcb.201211138
273. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172. doi:10.1084/jem.183.3.1161
274. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20(5):847–856. doi:10.1038/sj.leu.2404132
275. Reiche J, Pauli G, Ellerbrok H (2010) Differential expression of human endogenous retrovirus K transcripts in primary human melanocytes and melanoma cell lines after UV irradiation. Melanoma Res 20(5):435–440. doi:10.1097/CMR.0b013e32833c1b5d
276. Rijcken C, Soga O, Hennink W, van Nostrum C (2007) Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: an attractive tool for drug delivery. J Control Release 120(3):131–148. doi:10.1016/j.jconrel.2007.03.023
277. Roberts RL, Fine RE, Sandra A (1993) Receptor-mediated endocytosis of transferrin at the blood–brain barrier. J Cell Sci 104(Pt 2):521–532
278. Robertson C, Booth SA, Beniac DR, Coulthart MB, Booth TF, McNicol A (2006) Cellular prion protein is released on exosomes from activated platelets. Blood 107(10):3907–3911. doi:10.1182/blood-2005-02-0802
279. Roh Y, Lee J, Kiatwuthinon P, Hartman M, Cha J, Um S, Muller D, Luo D (2011) DNAsomes: multifunctional DNA-based nanocarriers. Small 7(1):74–78. doi:10.1002/smll.201000752
280. Russo I, Bubacco L, Greggio E (2012) Exosomes-associated neurodegeneration and progression of Parkinson’s disease. Am J Neurodegen Dis 1(3):217–225
281. Saksena S, Sun J, Chu T, Emr S (2007) ESCRTing proteins in the endocytic pathway. Trends Biochem Sci 32(12):561–573. doi:10.1016/j.tibs.2007.09.010
282. Saman S, Kim W, Raya M, Visnick Y, Miro S, Saman S, Jackson B, McKee AC, Alvarez VE, Lee NC, Hall GF (2012) Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem 287(6):3842–3849. doi:10.1074/jbc.M111.277061
283. Sawant RR, Jhaveri AM, Torchilin VP (2012) Immunomicelles for advancing personalized therapy. Adv Drug Deliv Rev 64(13):1436–1446. doi:10.1016/j.addr.2012.08.003
284. Schiera G, Proia P, Alberti C, Mineo M, Savettieri G, Di Liegro I (2007) Neurons produce FGF2 and VEGF and secrete them at least in part by shedding extracellular vesicles. J Cell Mol Med 11(6):1384–1394. doi:10.1111/j.1582-4934.2007.00100.x
285. Schneider A, Simons M (2013) Exosomes: vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res 352(1):33–47. doi:10.1007/s00441-012-1428-2
286. Sebbagh M, Renvoize C, Hamelin J, Riche N, Bertoglio J, Breard J (2001) Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol 3(4):346–352. doi:10.1038/35070019
287. Sekhon BS, Kamboj SR (2010a) Inorganic nanomedicine—Part 1. Nanomedicine 6(4):516–522. doi:10.1016/j.nano.2010.04.004
288. Sekhon BS, Kamboj SR (2010b) Inorganic nanomedicine—Part 2. Nanomedicine 6(5):612–618. doi:10.1016/j.nano.2010.04.003
289. Sharma P, Schiapparelli L, Cline HT (2013) Exosomes function in cell–cell communication during brain circuit development. Curr Opin Neurobiol 23(6):997–1004. doi:10.1016/j.conb.2013.08.005
290. Shin N, Jeong H, Kwon J, Heo HY, Kwon JJ, Yun HJ, Kim CH, Han BS, Tong Y, Shen J, Hatano T, Hattori N, Kim KS, Chang S, Seol W (2008) LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res 314(10):2055–2065. doi:10.1016/j.yexcr.2008.02.015
291. Shin-ichiro O, Akio I, Masahiko K (2013) Roles of exosomes and microvesicles in disease pathogenesis. Adv Drug Del Rev 65(3):398–401. doi:10.1016/j.addr.2012.07.019
292. Shu D, Shu Y, Haque F, Abdelmawla S, Guo P (2011) Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nat Nanotechnol 6(10):658–667. doi:10.1038/nnano.2011.105
293. Shu Y, Haque F, Shu D, Li W, Zhu Z, Kotb M, Lyubchenko Y, Guo P (2013a) Fabrication of 14 different RNA nanoparticles for specific tumor targeting without accumulation in normal organs. RNA 19(6):767–777. doi:10.1261/rna.037002.112
294. Shu Y, Shu D, Haque F, Guo P (2013b) Fabrication of pRNA nanoparticles to deliver therapeutic RNAs and bioactive compounds into tumor cells. Nat Protoc 8(9):1635–1659. doi:10.1038/nprot.2013.097
295. Shu Y, Pi F, Sharma A, Rajabi M, Haque F, Shu D, Leggas M, Evers BM, Guo P (2014) Stable RNA nanoparticles as potential new generation drugs for cancer therapy. Adv Drug Del Rev 66:74–89. doi:10.1016/j.addr.2013.11.006
296. Silva J, Garcia V, Zaballos A, Provencio M, Lombardia L, Almonacid L, Garcia JM, Dominguez G, Pena C, Diaz R, Herrera M, Varela A, Bonilla F (2011) Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J 37(3):617–623. doi:10.1183/09031936.00029610
297. Simak J, Gelderman MP, Yu H, Wright V, Baird AE (2006) Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome. J Thromb Haemost 4(6):1296–1302. doi:10.1111/j.1538-7836.2006.01911.x
298. Simona F, Laura S, Simona T, Riccardo A (2013) Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression: state of the art and new perspectives. Proteomics 13(10–11):1581–1594. doi:10.1002/pmic.201200398
299. Simons M, Raposo G (2009) Exosomes—vesicular carriers for intercellular communication. Curr Opin Cell Biol 21(4):575–581. doi:10.1016/j.ceb.2009.03.007
300. Skog J, Würdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M, Curry W, Carter B, Krichevsky A, Breakefield X (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476. doi:10.1038/ncb1800
301. Soekmadji C, Russell P, Nelson C (2013) Exosomes in prostate cancer: putting together the pieces of a puzzle. Cancers 5(4):1522–1544. doi:10.3390/cancers5041522
302. Son SJ, Bai X, Lee SB (2007a) Inorganic hollow nanoparticles and nanotubes in nanomedicine Part 1. Drug/gene delivery applications. Drug Discov Today 12(15–16):650–656. doi:10.1016/j.drudis.2007.06.002
303. Son SJ, Bai X, Lee SB (2007b) Inorganic hollow nanoparticles and nanotubes in nanomedicine Part 2: Imaging, diagnostic, and therapeutic applications. Drug Discov Today 12(15–16):657–663. doi:10.1016/j.drudis.2007.06.012
304. Soo CY, Song Y, Zheng Y, Campbell EC, Riches AC, Gunn-Moore F, Powis SJ (2012) Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells. Immunology 136(2):192–197. doi:10.1111/j.1365-2567.2012.03569.x
305. Spagnou S, Miller A, Keller M (2004) Lipidic carriers of siRNA: differences in the formulation, cellular uptake, and delivery with plasmid DNA. Biochemistry 43(42):13348–13356. doi:10.1021/bi048950a
306. Spuch C, Navarro C (2011) Liposomes for targeted delivery of active agents against neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). J Drug Deliv 2011:469679. doi:10.1155/2011/469679
307. Staruch R, Chopra R, Hynynen K (2011) Localised drug release using MRI-controlled focused ultrasound hyperthermia. Int J Hypertherm 27(2):156–171. doi:10.3109/02656736.2010.518198
308. Stoll E, Horner P, Rostomily R (2013) The impact of age on oncogenic potential: tumor-initiating cells and the brain microenvironment. Aging Cell 12(5):733–741. doi:10.1111/acel.12104
309. Subra C, Laulagnier K, Perret B, Record M (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89(2):205–212. doi:10.1016/j.biochi.2006.10.014
310. Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang H-G (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 18(9):1606–1614. doi:10.1038/mt.2010.105
311. Svensson K, Kucharzewska P, Christianson H, Sköld S, Löfstedt T, Johansson M, Mörgelin M, Bengzon J, Ruf W, Belting M (2011) Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc Natl Acad Sci USA 108(32):13147–13152. doi:10.1073/pnas.1104261108
312. Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL (2010) Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One 5(7):e11469. doi:10.1371/journal.pone.0011469
313. Tadokoro H, Umezu T, Ohyashiki K, Hirano T, Ohyashiki JH (2013) Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. J Biol Chem 288(48):34343–34351. doi:10.1074/jbc.M113.480822
314. Tai-Kin W, Nicolau C, Hofschneider PH (1980) Appearance of β-lactamase activity in animal cells upon liposome-mediated gene transfer. Gene 10(2):87–94. doi:10.1016/0378-1119(80)90126-2
315. Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK (2002) Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161(5):1869–1879
316. Tamboli IY, Barth E, Christian L, Siepmann M, Kumar S, Singh S, Tolksdorf K, Heneka MT, Lutjohann D, Wunderlich P, Walter J (2010) Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion. J Biol Chem 285(48):37405–37414. doi:10.1074/jbc.M110.149468
317. Tan A, De La Pena H, Seifalian AM (2010) The application of exosomes as a nanoscale cancer vaccine. Int J Nanomed 5:889–900. doi:10.2147/IJN.S13402
318. Tan A, Rajadas J, Seifalian A (2013) Exosomes as nano-theranostic delivery platforms for gene therapy. Adv Drug Del Rev 65(3):357–367. doi:10.1016/j.addr.2012.06.014
319. Tang S, Martinez LJ, Sharma A, Chai M (2006) Synthesis and characterization of water-soluble and photostable l-DOPA dendrimers. Org Lett 8(20):4421–4424. doi:10.1021/ol061449l
320. Taruscio D, Mantovani A (2004) Factors regulating endogenous retroviral sequences in human and mouse. Cytogenet Genome Res 105(2–4):351–362. doi:10.1159/000078208
321. Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110(1):13–21. doi:10.1016/j.ygyno.2008.04.033
322. Taylor DD, Akyol S, Gercel-Taylor C (2006) Pregnancy-associated exosomes and their modulation of T cell signaling. J Immunol 176(3):1534–1542
323. Taylor AR, Robinson MB, Gifondorwa DJ, Tytell M, Milligan CE (2007) Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Dev Neurobiol 67(13):1815–1829. doi:10.1002/dneu.20559
324. Taylor M, Moore S, Mourtas S, Niarakis A, Re F, Zona C, La Ferla B, Nicotra F, Masserini M, Antimisiaris SG, Gregori M, Allsop D (2011) Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer’s Abeta peptide. Nanomedicine 7(5):541–550. doi:10.1016/j.nano.2011.06.015
325. Templeton NS (2002) Cationic liposome-mediated gene delivery in vivo. Biosci Rep 22(2):283–295. doi:10.1023/A:1020142823595
326. Tennyson LD, Clemens B (2012) The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy. Chem Soc Rev 41(7):2885–2911. doi:10.1039/c2cs15260f
327. Theresa MA, Pieter RC (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Del Rev 65(1):36–48. doi:10.1016/j.addr.2012.09.037
328. Thery C (2011) Exosomes: secreted vesicles and intercellular communications. Biol Rep 3:1–5. doi:10.3410/b3-15
329. Théry C, Duban L, Segura E, Véron P, Lantz O, Amigorena S (2002a) Indirect activation of naïve CD4 + T cells by dendritic cell-derived exosomes. Nat Immunol 3(12):1156–1162
330. Théry C, Zitvogel L, Amigorena S (2002b) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2(8):569–579
331. Théry C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9(8):581–593. doi:10.1038/nri2567
332. Theunis C, Crespo-Biel N, Gafner V, Pihlgren M, López-Deber M, Reis P, Hickman D, Adolfsson O, Chuard N, Ndao D, Borghgraef P, Devijver H, Van Leuven F, Pfeifer A, Muhs A (2013) Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau P301L mice that model tauopathy. PLoS One 8(8):e72301. doi:10.1371/journal.pone.0072301.g005
333. Toledano Furman N, Lupu-Haber Y, Bronshtein T, Kaneti L, Letko N, Weinstein E, Baruch L, Machluf M (2013) Reconstructed stem cell nanoghosts: a natural tumor targeting platform. Nano Lett 13(7):3248–3255. doi:10.1021/nl401376w
334. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319(5867):1244–1247. doi:10.1126/science.1153124
335. Trumpfheller C, Longhi MP, Caskey M, Idoyaga J, Bozzacco L, Keler T, Schlesinger SJ, Steinman RM (2012) Dendritic cell-targeted protein vaccines: a novel approach to induce T-cell immunity. J Intern Med 271(2):183–192. doi:10.1111/j.1365-2796.2011.02496.x
336. Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH (2013) Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene 32(22):2747–2755. doi:10.1038/onc.2012.295
337. Upadhyay K, Bhatt A, Mishra A, Dwarakanath B, Jain S, Schatz C, Le Meins J-F, Farooque A, Chandraiah G, Jain A, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamma-benzyl l-glutamate)-b-hyaluronan polymersomes. Biomaterials 31(10):2882–2892. doi:10.1016/j.biomaterials.2009.12.043
338. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659. doi:10.1038/ncb1596
339. Valencia K, Luis-Ravelo D, Bovy N, Anton I, Martinez-Canarias S, Zandueta C, Ormazabal C, Struman I, Tabruyn S, Rebmann V, De Las Rivas J, Guruceaga E, Bandres E, Lecanda F (2014) miRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization. Mol Oncol 8(3):689–703. doi:10.1016/j.molonc.2014.01.012
340. Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, Corbelli A, Fais S, Parmiani G, Rivoltini L (2006) Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 66(18):9290–9298. doi:10.1158/0008-5472.can-06-1819
341. van der Vlist EJ, Nolte-’t Hoen EN, Stoorvogel W, Arkesteijn GJ, Wauben MH (2012) Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat Protoc 7(7):1311–1326. doi:10.1038/nprot.2012.065
342. van Dommelen S, Vader P, Lakhal S, Kooijmans SA, van Solinge W, Wood M, Schiffelers R (2012) Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in drug delivery. J Control Release 161(2):635–644. doi:10.1016/j.jconrel.2011.11.021
343. van Niel G, Porto-Carreiro I, Simoes S, Raposo G (2006) Exosomes: a common pathway for a specialized function. J Biochem 140(1):13–21. doi:10.1093/jb/mvj128
344. Vekrellis K, Xilouri M, Emmanouilidou E, Rideout H, Stefanis L (2011) Pathological roles of α-synuclein in neurological disorders. Lancet Neurol 10(11):1015–1025. doi:10.1016/S1474-4422(11)70213-7
345. Vella LJ, Sharples RA, Lawson VA, Masters CL, Cappai R, Hill AF (2007) Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J Pathol 211(5):582–590. doi:10.1002/path.2145
346. Vella L, Sharples R, Nisbet R, Cappai R, Hill A (2008) The role of exosomes in the processing of proteins associated with neurodegenerative diseases. Eur Biophys J 37(3):323–332. doi:10.1007/s00249-007-0246-z
347. Verderio C, Muzio L, Turola E, Bergami A, Novellino L, Ruffini F, Riganti L, Corradini I, Francolini M, Garzetti L, Maiorino C, Servida F, Vercelli A, Rocca M, Dalla Libera D, Martinelli V, Comi G, Martino G, Matteoli M, Furlan R (2012) Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Ann Neurol 72(4):610–624. doi:10.1002/ana.23627
348. Viaud S, Ploix S, Lapierre V, Thery C, Commere PH, Tramalloni D, Gorrichon K, Virault-Rocroy P, Tursz T, Lantz O, Zitvogel L, Chaput N (2011) Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-gamma. J Immunother 34(1):65–75. doi:10.1097/CJI.0b013e3181fe535b
349. Villarroya-Beltri C, Gutiérrez-Vázquez C (2013) Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 4:2980. doi:10.1038/ncomms3980
350. Vlassov A, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 7:940–948. doi:10.1016/j.bbagen.2012.03.017
351. Von Bartheld CS, Altick AL (2011) Multivesicular bodies in neurons: distribution, protein content, and trafficking functions. Prog Neurobiol 93(3):313–340. doi:10.1016/j.pneurobio.2011.01.003
352. Wahlgren J, De LKT, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 40(17):e130. doi:10.1093/nar/gks463
353. Walsh A, Yin H, Erben C, Wood M, Turberfield A (2011) DNA cage delivery to mammalian cells. ACS Nano 5(7):5427–5432. doi:10.1021/nn2005574
354. Wang H, Li F, Du C, Wang H, Mahato R, Huang Y (2014a) Doxorubicin and lapatinib combination nanomedicine for treating resistant breast cancer. Mol Pharma (in press). doi:10.1021/mp400687w
355. Wang M, Zhao C, Shi H, Zhang B, Zhang L, Zhang X, Wang S, Wu X, Yang T, Huang F, Cai J, Zhu Q, Zhu W, Qian H, Xu W (2014b) Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer. Br J Cancer 110(5):1199–1210. doi:10.1038/bjc.2014.14
356. Wang-Johanning F, Frost AR, Jian B, Epp L, Lu DW, Johanning GL (2003) Quantitation of HERV-K env gene expression and splicing in human breast cancer. Oncogene 22(10):1528–1535. doi:10.1038/sj.onc.1206241
357. Wasungu L, Hoekstra D (2006) Cationic lipids, lipoplexes and intracellular delivery of genes. J Control Release 116(2):255–264. doi:10.1016/j.jconrel.2006.06.024
358. Waterhouse DN, Tardi PG, Mayer LD, Bally MB (2001) A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles. Drug Saf 24(12):903–920. doi:10.0000/095372800232108
359. Wen Z, Yan Z, Hu K, Pang Z, Cheng X, Guo L, Zhang Q, Jiang X, Fang L, Lai R (2011) Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. J Control Release 151(2):131–138. doi:10.1016/j.jconrel.2011.02.022
360. Wiley RD, Gummuluru S (2006) Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proc Natl Acad Sci USA 103(3):738–743. doi:10.1073/pnas.0507995103
361. Wittmann J, Jäck H-M (2010) Serum microRNAs as powerful cancer biomarkers. Biochim Biophys Acta 1806(2):200–207. doi:10.1016/j.bbcan.2010.07.002
362. Wu J, Huang W, He Z (2013) Dendrimers as carriers for siRNA delivery and gene silencing: a review. Sci World J 2013:630654. doi:10.1155/2013/630654
363. Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, Slot JW, Geuze HJ, Stoorvogel W (2003) Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem 278(13):10963–10972. doi:10.1074/jbc.M207550200
364. Xia C-F, Boado R, Zhang Y, Chu C, Pardridge W (2008) Intravenous glial-derived neurotrophic factor gene therapy of experimental Parkinson’s disease with Trojan horse liposomes and a tyrosine hydroxylase promoter. J Gene Med 10(3):306–315. doi:10.1002/jgm.1152
365. Xiao D, Ohlendorf J, Chen Y, Taylor DD, Rai SN, Waigel S, Zacharias W, Hao H, McMasters KM (2012) Identifying mRNA, microRNA and protein profiles of melanoma exosomes. PLoS One 7(10):e46874. doi:10.1371/journal.pone.0046874
366. Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, Shang X, Zhang ZG, Chopp M (2012) Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 30(7):1556–1564. doi:10.1002/stem.1129
367. Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M (2013a) Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab 33(11):1711–1715. doi:10.1038/jcbfm.2013.152
368. Xin H, Li Y, Liu Z, Wang X, Shang X, Cui Y, Gang Zhang Z, Chopp M (2013b) Mir-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells. doi:10.1002/stem.1409
369. Xu W, Ling P, Zhang T (2013) Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs. J Drug Deliv 2013:340315. doi:10.1155/2013/340315
370. Yamada N, Nakagawa Y, Tsujimura N, Kumazaki M, Noguchi S, Mori T, Hirata I, Maruo K, Akao Y (2013) Role of intracellular and extracellular microRNA-92a in colorectal cancer. Transl Oncol 6(4):482–492. doi:10.1593/tlo.13280
371. Yang M, Chen J, Su F, Yu B, Su F, Lin L, Liu Y, Huang J-D, Song E (2011) Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol cancer 10:117. doi:10.1186/1476-4598-10-117
372. Yu X, Harris S, Levine A (2006) The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res 66(9):4795–4801. doi:10.1158/0008-5472.CAN-05-4579
373. Yu X, Riley T, Levine A (2009) The regulation of the endosomal compartment by p53 the tumor suppressor gene. FEBS J 276(8):2201–2212. doi:10.1111/j.1742-4658.2009.06949.x
374. Yu Y, Pang Z, Lu W, Yin Q, Gao H, Jiang X (2012) Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery. Pharmaceut Res 29(1):83–96. doi:10.1007/s11095-011-0513-7
375. Yu L, Yang F, Jiang L, Chen Y, Wang K, Xu F, Wei Y, Cao X, Wang J, Cai Z (2013) Exosomes with membrane-associated TGF-beta1 from gene-modified dendritic cells inhibit murine EAE independently of MHC restriction. Eur J Immunol 43(9):2461–2472. doi:10.1002/eji.201243295
376. Yuyama K, Yamamoto N, Yanagisawa K (2008) Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation. J Neurochem 105(1):217–224. doi:10.1111/j.1471-4159.2007.05128.x
377. Yuyama K, Sun H, Mitsutake S, Igarashi Y (2012) Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J Biol Chem 287(14):10977–10989. doi:10.1074/jbc.M111.324616
378. Zeelenberg IS, Ostrowski M, Krumeich S, Bobrie A, Jancic C, Boissonnas A, Delcayre A, Le Pecq JB, Combadière B, Amigorena S, Théry C (2008) Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res 68(4):1228–1235. doi:10.1158/0008-5472.can-07-3163
379. Zhan R, Leng X, Liu X, Wang X, Gong J, Yan L (2009) Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes. Biochem Biophys Res Commun 387(2):229–233. doi:10.1016/j.bbrc.2009.06.095
380. Zhan C, Wei X, Qian J, Feng L, Zhu J, Lu W (2012) Co-delivery of TRAIL gene enhances the anti-glioblastoma effect of paclitaxel in vitro and in vivo. J Control Release 160(3):630–636. doi:10.1016/j.jconrel.2012.02.022
381. Zhang Y, Zhang Y, Bryant J, Charles A, Boado R (2004) Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer. Clin Cancer Res 10(11):3667–3677. doi:10.1158/1078-0432.CCR-03-0740
382. Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, Sun F, Lu J, Yin Y, Cai X, Sun Q, Wang K, Ba Y, Wang Q, Wang D, Yang J, Liu P, Xu T, Yan Q, Zhang J, Zen K, Zhang C-Y (2010) Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell 39(1):133–144. doi:10.1016/j.molcel.2010.06.010
383. Zhang X–X, McIntosh T, Grinstaff M (2012) Functional lipids and lipoplexes for improved gene delivery. Biochimie 94(1):42–58. doi:10.1016/j.biochi.2011.05.005
384. Zhu J, Shi X (2013) Dendrimer-based nanodevices for targeted drug delivery applications. J Mater Chem B 1(34):4199. doi:10.1039/c3tb20724b
385. Zhu G, Hu R, Zhao Z, Chen Z, Zhang X, Tan W (2013) Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications. J Am Chem Soc 135(44):16438–16445. doi:10.1021/ja406115e
386. Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19(10):1769–1779. doi:10.1038/mt.2011.164
387. Zia ur R, Dick H, Inge SZ (2013) Mechanism of polyplex- and lipoplex-mediated delivery of nucleic acids: real-time visualization of transient membrane destabilization without endosomal lysis. ACS Nano 7(5):3767–3777. doi:10.1021/nn3049494
388. Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM (2010) Exosomes: fit to deliver small RNA. Commun Integr Biol 3(5):447–450. doi:10.4161/cib.3.5.12339
389. Zwaal RF, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89(4):1121–1132