Enabling cytoplasmic delivery and organelle targeting by surface modification of nanocarriers

Nanomedicine

Volumn 10, Issue 12, 2015, Pages 1923-1940

  Parodi, Alessandro ^a,b   Corbo, Claudia ^b   Cevenini, Armando ^c,d   Molinaro, Roberto ^a,e   Palomba, Roberto ^b   Pandolfi, Laura ^a,f   Agostini, Marco ^e   Salvatore, Francesco ^b,d   Tasciotti, Ennio ^a  

^a HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^b IRCCS SDN   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

^e UNIVERSITY OF PADOVA   (Italy)

^f University of Chinese Academy of Science   (China)

Author keywords

biological barriers; cell surface modifications; intracellular targeting; nanocarriers; nanomedicine

Indexed keywords

CELL PENETRATING PEPTIDE; LIPID; NANOCARRIER; POLYMER; POLYPEPTIDE ANTIBIOTIC AGENT; BIOMATERIAL; NANOCAPSULE;

CELL NUCLEUS; CELL SURFACE; CHEMICAL MODIFICATION; CONJUGATION; CYTOPLASM; DEGRADATION; ENDOPLASMIC RETICULUM; ENDOSOME; HUMAN; INTERNALIZATION; MITOCHONDRION; PH; PRIORITY JOURNAL; REVIEW; ANIMAL; CELL ORGANELLE; CHEMISTRY; DRUG DESIGN; MATERIALS TESTING; SURFACE PROPERTY; SYNTHESIS; ULTRASTRUCTURE;

ANIMALS; COATED MATERIALS, BIOCOMPATIBLE; CYTOPLASM; DRUG DESIGN; HUMANS; MATERIALS TESTING; NANOCAPSULES; ORGANELLES; SURFACE PROPERTIES;

EID: 84936972741     PISSN: 17435889     EISSN: 17486963     Source Type: Journal    
DOI: 10.2217/nnm.15.39     Document Type: Review

References (178)

1. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 4(2), 145-160 (2005).
2. Davis ME. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7(9), 771-782 (2008).
3. Lammers T, Hennink WE, Storm G. Tumour-Targeted nanomedicines: principles and practice. Br. J. Cancer 99(3), 392-397 (2008).
4. Swami A, Shi J, Gadde S, Votruba AR, Kolishetti N, Farokhzad OC. Nanoparticles for targeted and temporally controlled drug delivery. In: Multifunctional Nanoparticles for Drug Delivery Applications. Springer, NY, USA, 9-29 (2012).
5. Wang J, Lu Z, Wientjes MG, Au JLS. Delivery of siRNA therapeutics: barriers and carriers. AAPS J. 12(4), 492-503 (2010).
6. Hoffman AS. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 64, 18-23 (2012).
7. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev. 64, 49-60 (2012).
8. Hoffman AS. Stimuli-responsive polymers: biomedical applications and challenges for clinical translation. Adv. Drug Deliv. Rev. 65(1), 10-16 (2013).
9. Petros RA, Desimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9(8), 615-627 (2010).
10. Gratton SE, Ropp PA, Pohlhaus PD, et al. The effect of particle design on cellular internalization pathways. Proc. Natl Acad. Sci. 105(33), 11613-11618 (2008).
11. Albanese A, Tang PS, Chan WC. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Ann. Rev. Biomed. Eng. 14, 1-16 (2012).
12. Varkouhi AK, Scholte M, Storm G, Haisma HJ. Endosomal escape pathways for delivery of biologicals. J. Control. Release 151(3), 220-228 (2011).
13. Mellman I. Endocytosis and molecular sorting. Annu. Rev. Cell. Dev. Biol. 12, 575-625 (1996).
14. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Molecular Cell Biology (4th Edition). W H Freeman, NY, USA (2000).
15. Molinaro R, Wolfram J, Federico C, et al. Polyethylenimine and chitosan carriers for the delivery of RNA interference effectors. Expert Opin. Drug Deliv. 10(12), 1653-1668 (2013).
16. Madani F, Lindberg S, Langel U, Futaki S, Graslund A. Mechanisms of cellular uptake of cell-penetrating peptides. J. Biophys. doi:10.1155/2011/414729 (2011) (Epub ahead of print).
17. Koren E, Torchilin VP. Cell-penetrating peptides: breaking through to the other side. Trends Mol. Med. 18(7), 385-393 (2012).
18. Sandgren S, Cheng F, Belting M. Nuclear targeting of macromolecular polyanions by an HIV-Tat derived peptide Role for cell-surface proteoglycans. J. Biol. Chem. 277(41), 38877-38883 (2002).
19. Console S, Marty C, Garcia-Echeverria C, Schwendener R, Ballmer-Hofer K. Antennapedia and HIV transactivator of transcription (TAT) protein transduction domains promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. J. Biol. Chem. 278(37), 35109-35114 (2003).
20. Lindgren M, Hallbrink M, Prochiantz A, Langel U. Cellpenetrating peptides. Trends Pharmacol. Sci. 21(3), 99-103 (2000).
21. Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu. Rev. Biomed. Eng. 8, 343-375 (2006).
22. Sakhrani NM, Padh H. Organelle targeting: third level of drug targeting. Drug Des. Devel. Ther. 7, 585-599 (2013).
23. Maniti O, Blanchard E, Trugnan G, Lamaziere A, Ayala-Sanmartin J. Metabolic energy-independent mechanism of internalization for the cell penetrating peptide penetratin. Int. J. Biochem. Cell Biol. 44(6), 869-875 (2012).
24. Patel LN, Zaro JL, Shen W-C. Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives. Pharmaceut. Res. 24(11), 1977-1992 (2007).
25. Kaplan IM, Wadia JS, Dowdy SF. Cationic TAT peptide transduction domain enters cells by macropinocytosis. J. Control. Release 102(1), 247-253 (2005).
26. Duchardt F, Fotin-Mleczek M, Schwarz H, Fischer R, Brock R. A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic 8(7), 848-866 (2007).
27. Madani F, Lindberg S, Langel U, Futaki S, Graslund A. Mechanisms of cellular uptake of cell-penetrating peptides. J. Biophys. 2011, 414729
28. Maiolo JR, Ferrer M, Ottinger EA. Effects of cargo molecules on the cellular uptake of arginine-rich cellpenetrating peptides. Biochim. Biophys. Acta 1712(2), 161-172 (2005).
29. Yang X, Chen Q-Y, Li X, Gao J. Functional ionic liquids induced the formation of mitochondria targeted fluorescent core-shell ellipsoidal nanoparticles with anticancer properties. Colloids Surf. B. Biointerfaces 98, 91-96 (2012).
30. Krpeticc ZE, Saleemi S, Prior IA, See V, Qureshi R, Brust M. Negotiation of intracellular membrane barriers by TATmodified gold nanoparticles. ACS Nano 5(6), 5195-5201 (2011).
31. Liu J, Zhao Y, Guo Q, et al. TAT-modified nanosilver for combating multidrug-resistant cancer. Biomaterials 33(26), 6155-6161 (2012).
32. Tian X-H, Wei F, Wang T-X, et al. Blood-brain barrier transport of Tat peptide and polyethylene glycol decorated gelatin-siloxane nanoparticle. Mater. Lett. 68, 94-96 (2012).
33. Qin Y, Chen HL, Yuan WM, et al. Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery. Int. J. Pharmaceut. 419(1-2), 85-95 (2011).
34. Laquintana V, Trapani A, Denora N, Wang F, Gallo JM, Trapani G. New strategies to deliver anticancer drugs to brain tumors. Expert Opin. Drug Deliv. 6(10), 1017-1032 (2009).
35. Jain A, Yadav BK, Chugh A. Marine antimicrobial peptide tachyplesin as an efficient nanocarrier for macromolecule delivery in plant and mammalian cells. FEBS J. 282(4), 732-745 (2015).
36. Zasloff M. Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc. Natl Acad. Sci. USA 84(15), 5449-5453 (1987).
37. Pushpanathan M, Gunasekaran P, Rajendhran J. Antimicrobial peptides: versatile biological properties. Int. J. Pept. doi:10.1155/2013/675391 (2013) (Epub ahead of print).
38. Vale N, Aguiar L, Gomes P. Antimicrobial peptides: a new class of antimalarial drugs?. Front. Pharmacol. 5, 275 (2014).
39. Scudiero O, Galdiero S, Cantisani M, et al. Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity. Antimicrob. Agents Chemother. 54(6), 2312-2322 (2010).
40. Scudiero O, Galdiero S, Nigro E, et al. Chimeric betadefensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines. Antimicrob. Agents Chemother. 57(4), 1701-1708 (2013).
41. Colavita I, Nigro E, Sarnataro D, et al. Membrane protein 4F2/CD98 is a cell surface receptor involved in the internalization and trafficking of human β-defensin 3 in epithelial cells. Chem. Biol. 22(2), 217-228 (2015).
42. Golubeva OY, Shamova O, Orlov D, et al. Synthesis and study of antimicrobial activity of bioconjugates of silver nanoparticles and endogenous antibiotics. Glass Phys. Chem. 37(1), 78-84 (2011).
43. Yang K, Gitter B, Ruger R, et al. Antimicrobial peptidemodified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy. Photochem. Photobiol. Sci. 10(10), 1593-1601 (2011).
44. Pacor S, Giangaspero A, Bacac M, Sava G, Tossi A. Analysis of the cytotoxicity of synthetic antimicrobial peptides on mouse leucocytes: implications for systemic use. J. Antimicrob. Chemother. 50(3), 339-348 (2002).
45. Hancock RE. Cationic peptides: effectors in innate immunity and novel antimicrobials. Lancet Infect. Dis. 1(3), 156-164 (2001).
46. Wang L, Liu Y, Li W, et al Selective targeting of gold nanorods at the mitochondria of cancer cells: implications for cancer therapy. Nano Lett. 11(2), 772-780 (2010).
47. Pfeifer A, Verma IM. Gene therapy: Promises and problems. Annu. Rev. Gen. Hum. Genet. 2, 177-211 (2001).
48. Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat. Med. 7(1), 33-40 (2001).
49. Benjaminsen RV, Mattebjerg MA, Henriksen JR, Moghimi SM, Andresen TL. The possible proton sponge effect of polyethylenimine (PEI) does not include change in lysosomal pH. Mol. Ther. 21(1), 149-157 (2013).
50. Nel AE, Madler L, Velegol D, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mat. 8(7), 543-557 (2009).
51. Godbey WT, Wu KK, Mikos AG. Poly(ethylenimine)-mediated gene delivery affects endothelial cell function and viability. Biomaterials 22(5), 471-480 (2001).
52. Xia TA, Kovochich M, Liong M, et al. Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs. ACS Nano 3(10), 3273-3286 (2009).
53. Dufes C, Uchegbu IF, Schatzlein AG. Dendrimers in gene delivery. Adv. Drug Deliv. Rev. 57(15), 2177-2202 (2005).
54. Radu DR, Lai CY, Jeftinija K, Rowe EW, Jeftinija S, Lin VSY. A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent. J. Am. Chem. Soc. 126(41), 13216-13217 (2004).
55. Vicent MJ, Dieudonne L, Carbajo RJ, Pineda-Lucena A. Polymer conjugates as therapeutics: future trends, challenges and opportunities. Expert Opin. Drug Deliv. 5(5), 593-614 (2008).
56. Sun JT, Hong CY, Pan CY. Fabrication of PDEAEMA-coated mesoporous silica nanoparticles and pH-responsive controlled release. J. Phys. Chem. C. 114(29), 12481-12486 (2010).
57. Marek SR, Conn CA, Peppas NA. Cationic nanogels based on diethylaminoethyl methacrylate. Polymer 51(6), 1237-1243 (2010).
58. You YZ, Manickam DS, Zhou QH, Oupicky D. Reducible poly(2-dimethylaminoethyl methaerylate): synthesis, cytotoxicity, and gene delivery activity. J. Control. Release 122(3), 217-225 (2007).
59. Gao Q, Xu Y, Wu D, Sun YH, Li XA. pH-Responsive drug release from polymer-coated mesoporous silica spheres. J. Phys. Chem. C 113(29), 12753-12758 (2009).
60. Midoux P, Pichon C, Yaouanc JJ, JaffraS PA. Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers. Br. J. Pharm. 157(2), 166-178 (2009).
61. Liang W, Lam JK. Endosomal escape pathways for nonviral nucleic acid delivery systems. (2012). www.intechopen.com/books
62. Wu H, Zhu L, Torchilin VP. pH-sensitive poly(histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery. Biomaterials 34(4), 1213-1222 (2013).
63. Gillard M, Jia ZF, Jia J, et al. Intracellular trafficking pathways for nuclear delivery of plasmid DNA complexed with highly efficient endosome escape polymers. Biomacromolecules 15(10), 3569-3576 (2014).
64. Hong SP, Leroueil PR, Janus EK, et al. Interaction of polycationic polymers with supported lipid bilayers and cells: nanoscale hole formation and enhanced membrane permeability. Bioconjug. Chem. 17(3), 728-734 (2006).
65. Convertine AJ, Diab C, Prieve M, et al. pH-responsive polymeric micelle carriers for siRNA drugs. Biomacromolecules 11(11), 2904-2911 (2010).
66. Lackey CA, Press OW, Hoffman AS, Stayton PS. A biomimetic pH-responsive polymer directs endosomal release and intracellular delivery of an endocytosed antibody complex. Bioconjug. Chem. 13(5), 996-1001 (2002).
67. El-Sayed MEH, Hoffman AS, Stayton PS. Rational design of composition and activity correlations for pH-sensitive and glutathione-reactive polymer therapeutics. J. Control. Release 101(1-3), 47-58 (2005).
68. Meier O, Greber UF. Adenovirus endocytosis. J. Gene Med. 6, S152-S163 (2004).
69. Hogle JM. Poliovirus cell entry: common structural themes in viral cell entry pathways. Annu. Rev. Microbiol. 56, 677-702 (2002).
70. Mandal M, Lee KD. Listeriolysin O-liposome-mediated cytosolic delivery of macromolecule antigen in vivo: enhancement of antigen-specific cytotoxic T lymphocyte frequency, activity, and tumor protection. Biochim. Biophys. Acta Biomembranes 1563(1-2), 7-17 (2002).
71. Parente RA, Nir S, Szoka FC. pH-dependent fusion of phosphatidylcholine small vesicles-induction by a synthetic amphipathic peptide. J. Biol. Chem. 263(10), 4724-4730 (1988).
72. Kullberg M, Owens JL, Mann K. Listeriolysin O enhances cytoplasmic delivery by Her-2 targeting liposomes. J. Drug Target. 18(4), 313-320 (2010).
73. Ogris M, Carlisle RC, Bettinger T, Seymour LW. Melittin enables efficient vesicular escape and enhanced nuclear access of nonviral gene delivery vectors. J. Biol. Chem. 276(50), 47550-47555 (2001).
74. Dempsey CE. The actions of melittin on membranes. Biochim. Biophys. Acta 1031(2), 143-161 (1990).
75. Boeckle S, Fahrmeir J, Roedl W, Ogris M, Wagner E. Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexes. J. Control. Release 112(2), 240-248 (2006).
76. Kakimoto S, Hamada T, Komatsu Y, et al. The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection. Biomaterials 30(3), 402-408 (2009).
77. Oliveira S, Van Rooy I, Kranenburg O, Storm G, Schiffelers RM. Fusogenic peptides enhance endosomal escape improving siRNA-induced silencing of oncogenes. Int. J. Pharmaceut. 331(2), 211-214 (2007).
78. Mastrobattista E, Koning GA, Van Bloois L, Filipe ACS, Jiskoot W, Storm G. Functional characterization of an endosome-disruptive peptide and its application in cytosolic delivery of immunoliposome-entrapped proteins. J. Biol. Chem. 277(30), 27135-27143 (2002).
79. Funhoff AM, Van Nostrum CF, Janssen APCA, Fens MHaM, Crommelin DJA, Hennink WE. Polymer sidechain degradation as a tool to control the destabilization of polyplexes. Pharmaceut. Res. 21(1), 170-176 (2004).
80. Funhoff AM, Van Nostrum CF, Lok MC, Fretz MM, Crommelin DJA, Hennink WE. Poly(3-guanidinopropyl methacrylate): a novel cationic polymer for gene delivery. Bioconjug. Chem. 15(6), 1212-1220 (2004).
81. Jiang X, Lok MC, Hennink WE. Degradable-brushed pHEMA-pDMAEMA synthesized via ATRP and click chemistry for gene delivery. Bioconjug. Chem. 18(6), 2077-2084 (2007).
82. Min SH, Lee DC, Lim MJ, et al. A composite gene delivery system consisting of polyethylenimine and an amphipathic peptide KALA. J. Gene Med. 8(12), 1425-1434 (2006).
83. Futaki S, Masui Y, Nakase I, et al. Unique features of a pHsensitive fusogenic peptide that improves the transfection efficiency of cationic liposomes. J. Gene Med. 7(11), 1450-1458 (2005).
84. Sasaki K, Kogure K, Chaki S, et al. An artificial viruslike nano carrier system: enhanced endosomal escape of nanoparticles via synergistic action of pH-sensitive fusogenic peptide derivatives. Anal. Bioanal. Chem. 391(8), 2717-2727 (2008).
85. Kakudo T, Chaki S, Futaki S, et al. Transferrin-modified liposomes equipped with a pH-sensitive fusogenic peptide: an artificial viral-like delivery system. Biochemistry 43(19), 5618-5628 (2004).
86. Ulrich AS. Biophysical aspects of using liposomes as delivery vehicles. Biosci. Rep. 22(2), 129-150 (2002).
87. Mo R, Sun Q, Li N, Zhang C. Intracellular delivery and antitumor effects of pH-sensitive liposomes based on zwitterionic oligopeptide lipids. Biomaterials 34(11), 2773-2786 (2013).
88. Liu Q, Jiang QQ, Yi WJ, et al. Novel imidazolefunctionalized cyclen cationic lipids: synthesis and application as non-viral gene vectors. Bioorg. Med. Chem. 21(11), 3105-3113 (2013).
89. Billiet L, Gomez JP, Berchel M, et al. Gene transfer by chemical vectors, and endocytosis routes of polyplexes, lipoplexes and lipopolyplexes in a myoblast cell line. Biomaterials 33(10), 2980-2990 (2012).
90. Goncalves C, Berchel M, Gosselin M-P, et al. Lipopolyplexes comprising imidazole/imidazolium lipophosphoramidate, histidinylated polyethyleneimine and siRNA as efficient formulation for siRNA transfection. Int. J. Pharmaceut. 460(1), 264-272 (2013).
91. Cooper GM, Hausman RE. The Cell. ASM Press, Washington, USA (2000).
92. Gorlich D, Kutay U. Transport between the cell nucleus and the cytoplasm. Annu. Rev. Cell Devel. Biol. 15(1), 607-660 (1999).
93. Parks SB, Kushner JD, Nauman D, et al. Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy. Am. Heart J. 156(1), 161-169 (2008).
94. Muchir A, Bonne G, Van Der Kooi AJ, et al. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum. Mol. Genet. 9(9), 1453-1459 (2000).
95. Peters MF, Nucifora Jr FC, Kushi J, et al. Nuclear targeting of mutant Huntingtin increases toxicity. Mol. Cell. Neurosci. 14(2), 121-128 (1999).
96. Zhang LW, Monteiro-Riviere NA. Mechanisms of quantum dot nanoparticle cellular uptake. Toxicol. Sci. 110(1), 138-155 (2009).
97. Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev. 55(3), 329-347 (2012).
98. Asati A, Santra S, Kaittanis C, Perez JM. Surface-chargedependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano 4(9), 5321-5331 (2010).
99. Tkachenko AG, Xie H, Coleman D, et al. Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. J. Am. Chem. Soc. 125(16), 4700-4701 (2003).
100. Suntharalingam M, Wente SR. Peering through the pore: nuclear pore complex structure, assembly, and function. Dev. Cell 4(6), 775-789 (2003).
101. Cook A, Bono F, Jinek M, Conti E. Structural biology of nucleocytoplasmic transport. Annu. Rev. Biochem. 76, 647-671 (2007).
102. Kubitscheck U, Grunwald D, Hoekstra A, et al. Nuclear transport of single molecules dwell times at the nuclear pore complex. J. Cell Biol. 168(2), 233-243 (2005).
103. Raoof M, Mackeyev Y, Cheney MA, Wilson LJ, Curley SA. Internalization of C60 fullerenes into cancer cells with accumulation in the nucleus via the nuclear pore complex. Biomaterials 33(10), 2952-2960 (2012).
104. Biswas S, Dodwadkar NS, Deshpande PP, Torchilin VP. Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo. J. Control Release 159(3), 393-402 (2012).
105. Liu J-N, Bu W, Pan L-M, et al. Simultaneous nuclear imaging and intranuclear drug delivery by nuclear-Targeted multifunctional upconversion nanoprobes. Biomaterials 33(29), 7282-7290 (2012).
106. Pan L, He Q, Liu J, et al. Nuclear-Targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J. Am. Chem. Soc. 134(13), 5722-5725 (2012).
107. Masuda T, Akita H, Nishio T, et al. Development of lipid particles targeted via sugar-lipid conjugates as novel nuclear gene delivery system. Biomaterials 29(6), 709-723 (2008).
108. Niikura K, Sekiguchi S, Nishio T, et al. Oligosaccharidemediated nuclear transport of nanoparticles. ChemBioChem. 9(16), 2623-2627 (2008).
109. Eguchi A, Furusawa H, Yamamoto A, et al. Optimization of nuclear localization signal for nuclear transport of DNAencapsulating particles. J. Control. Release 104(3), 507-519 (2005).
110. Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E. A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc. Natl Acad. Sci. 99(11), 7444-7449 (2002).
111. Kang B, Mackey MA, El-Sayed MA. Nuclear targeting of gold nanoparticles in cancer cells induces DNA damage, causing cytokinesis arrest and apoptosis. J. Am. Chem. Soc. 132(5), 1517-1519 (2010).
112. Mackey MA, Saira F, Mahmoud MA, El-Sayed MA. Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages. Bioconjug. Chem. 24(8), 897-906 (2013).
113. Ziegler A, Seelig J. High affinity of the cell-penetrating peptide HIV-1 Tat-PTD for DNA. Biochemistry 46(27), 8138-8145 (2007).
114. Pan L, Liu J, He Q, Wang L, Shi J. Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles. Biomaterials 34(11), 2719-2730 (2013).
115. Misra R, Sahoo SK. Intracellular trafficking of nuclear localization signal conjugated nanoparticles for cancer therapy. Eur. J. Pharmaceut. Sci. 39(1), 152-163 (2010).
116. Jana A, Saha B, Banerjee DR, et al. Photocontrolled nucleartargeted drug delivery by single component photoresponsive fluorescent organic nanoparticles of acridin-9-methanol. Bioconjug. Chem. 24(11), 1828-1839 (2013).
117. Grandinetti G, Reineke TM. Exploring the mechanism of plasmid DNA nuclear internalization with polymer-based vehicles. Mol. Pharmaceut. 9(8), 2256-2267 (2012).
118. Grandinetti G, Smith AE, Reineke TM. Membrane and nuclear permeabilization by polymeric pDNA vehicles: efficient method for gene delivery or mechanism of cytotoxicity?. Mol. Pharmaceut. 9(3), 523-538 (2012).
119. Yuan Y, Chen S, Paunesku T, et al. Epidermal growth factor receptor targeted nuclear delivery and high-resolution whole cell X-ray imaging of Fe3O4@TiO2 nanoparticles in cancer cells. ACS Nano 7(12), 10502-10517 (2013).
120. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Integrating cells into tissues. In: Molecular Cell Biology (4th Edition). W. H. Freeman and Company NY, USA (2000).
121. Davidson SM, Duchen MR. Effects of NO on mitochondrial function in cardiomyocytes: pathophysiological relevance. Cardiovasc. Res. 71(1), 10-21 (2006).
122. Dias N, Bailly C. Drugs targeting mitochondrial functions to control tumor cell growth. Biochem. Pharmacol. 70(1), 1-12 (2005).
123. Kwong JQ, Beal MF, Manfredi G. The role of mitochondria in inherited neurodegenerative diseases. J. Neurochem. 97(6), 1659-1675 (2006).
124. Liu J, Ames BN. Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease. Nutr. Neurosci. 8(2), 67-89 (2005).
125. Wiederkehr A, Wollheim CB. Minireview: implication of mitochondria in insulin secretion and action. Endocrinology 147(6), 2643-2649 (2006).
126. Riganti C, Rolando B, Kopecka J, et al. Mitochondrialtargeting nitrooxy-doxorubicin: a new approach to overcome drug resistance. Mol. Pharm. 10(1), 161-174 (2012).
127. Han M, Vakili MR, Soleymani Abyaneh H, Molavi O, Lai R, Lavasanifar A. Mitochondrial delivery of doxorubicin via triphenylphosphine modification for overcoming drug resistance in MDA-MB-435/DOX cells. Mol. Pharm. 11(8), 2640-2649 (2014).
128. Zhao K, Zhao G-M, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J. Biol. Chem. 279(33), 34682-34690 (2004).
129. Yoong SL, Wong BS, Zhou QL, et al. Enhanced cytotoxicity to cancer cells by mitochondria-Targeting MWCNTs containing platinum (IV) prodrug of cisplatin. Biomaterials 35(2), 748-759 (2014).
130. Murphy MP. Targeting lipophilic cations to mitochondria. Biochim. Biophys. Acta (BBA)-Bioenergetics 1777(7), 1028-1031 (2008).
131. Marrache S, Dhar S. Engineering of blended nanoparticle platform for delivery of mitochondria-Acting therapeutics. Proc. Natl Acad. Sci. 109(40), 16288-16293 (2012).
132. Hoshino A, Fujioka K, Oku T, et al. Quantum dots targeted to the assigned organelle in living cells. Microbiol. Immunol. 48(12), 985-994 (2004).
133. Weissig V, Lasch J, Erdos G, Meyer HW, Rowe TC, Hughes J. DQAsomes: a novel potential drug and gene delivery system made from dequalinium™. Pharmaceut. Res. 15(2), 334-337 (1998).
134. D'souza GG, Boddapati SV, Weissig V. Mitochondrial leader sequence-plasmid DNA conjugates delivered into mammalian cells by DQAsomes co-localize with mitochondria. Mitochondrion 5(5), 352-358 (2005).
135. Weiss MJ, Wong JR, Ha CS, et al. Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation. Proc. Natl Acad. Sci. 84(15), 5444-5448 (1987).
136. Wang X-X, Li Y-B, Yao H-J, et al. The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells. Biomaterials 32(24), 5673-5687 (2011).
137. Yamada Y, Akita H, Kamiya H, et al. MITO-Porter: a liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. Biochim. Biophys. Acta (BBA)-Biomembranes 1778(2), 423-432 (2008).
138. Yasuzaki Y, Yamada Y, Harashima H. Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes. Biochem. Biophys. Res. Commun. 397(2), 181-186 (2010).
139. Yamada Y, Furukawa R, Yasuzaki Y, Harashima H. Dual function MITO-Porter, a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery. Mol. Ther. 19(8), 1449-1456 (2011).
140. Agemy L, Friedmann-Morvinski D, Kotamraju VR, et al. Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. Proc. Natl Acad. Sci. 108(42), 17450-17455 (2011).
141. Kim D, Lee ES, Oh KT, Gao ZG, Bae YH Doxorubicinloaded polymeric micelle overcomes multidrug resistance of cancer by double-Targeting folate receptor and early endosomal pH. Small 4(11), 2043-2050 (2008).
142. Midoux P, Pichon C, Yaouanc JJ, Jaffres PA. Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers. Br. J. Pharm. 157(2), 166-178 (2009).
143. Wen Y, Guo Z, Du Z, et al. Serum tolerance and endosomal escape capacity of histidine-modified pDNA-loaded complexes based on polyamidoamine dendrimer derivatives. Biomaterials 33(32), 8111-8121 (2012).
144. Lee ES, Na K, Bae YH Super pH-sensitive multifunctional polymeric micelle. Nano lett. 5(2), 325-329 (2005).
145. Kim I, Xu WJ, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 7(12), 1013-1030 (2008).
146. Ma YJ, Hendershot LM. ER chaperone functions during normal and stress conditions. J. Chem. Neuroanat. 28(1-2), 51-65 (2004).
147. Xu CY, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest. 115(10), 2656-2664 (2005).
148. Neve EPA, Ingelman-Sundberg M. Cytochrome P450 proteins: retention and distribution from the endoplasmic reticulum. Curr. Opin. Drug Discov. Devel. 13(1), 78-85 (2010).
149. Unterberger U, Hoftberger R, Gelpi E, Flicker H, Budka H, Voigtlander T. Endoplasmic reticulum stress features are prominent in Alzheimer disease but not in prion diseases in vivo. J. Neuropathol. Exp. Neurol. 65(4), 348-357 (2006).
150. Bi MX, Naczki C, Koritzinsky M, et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J. 24(19), 3470-3481 (2005).
151. Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306(5695), 457-461 (2004).
152. Glembotski CC. The role of the unfolded protein response in the heart. J. Mol. Cell. Cardiol. 44(3), 453-459 (2008).
153. Capitani M, Sallese M. The KDEL receptor: new functions for an old protein. Febs Lett. 583(23), 3863-3871 (2009).
154. Acharya S, Hill RA. High efficacy gold-KDEL peptidesiRNA nanoconstruct-mediated transfection in C2C12 myoblasts and myotubes. Nanomedicine 10(2), 329-337 (2014).
155. Delie F, Petignat P, Cohen M. GRP78-Targeted nanotherapy against castrate-resistant prostate cancer cells expressing membrane GRP78. Target Oncol. 8(4), 225-230
156. Rajendran L, Knolker HJ, Simons K. Subcellular targeting strategies for drug design and delivery. Nat. Rev. Drug Discov. 9(1), 29-42 (2010).
157. Leifert JA, Rodriguez-Carreno MP, Rodriguez F, Whitton JL. Targeting plasmid-encoded proteins to the antigen presentation pathways. Immunol. Rev. 199(1), 40-53 (2004).
158. Hayashi A, Wakita H, Yoshikawa T, et al. A strategy for efficient cross-presentation of CTL-epitope peptides leading to enhanced induction of in vivo tumor immunity. J. Control. Release 117(1), 11-19 (2007).
159. Swift LL. Assembly of very-low-density lipoproteins in ratliver-A study of nascent particles recovered from the rough endoplasmic-reticulum. J. Lipid Res. 36(3), 395-406 (1995).
160. Pollock S, Antrobus R, Newton L, et al. Uptake and trafficking of liposomes to the endoplasmic reticulum. FASEB J. 24(6), 1866-1878 (2010).
161. Greish K. Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting. In: Cancer Nanotechnology. Springer, NY, USA, 25-37 (2010).
162. Modi S, Prakash Jain J, Domb A, Kumar N. Exploiting EPR in polymer drug conjugate delivery for tumor targeting. Curr. Pharm. Des. 12(36), 4785-4796 (2006).
163. Roberts M, Bentley M, Harris J. Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev. 54(4), 459-476 (2002).
164. Sacchetti C, Motamedchaboki K, Magrini A, et al. Surface polyethylene glycol conformation influences the protein corona of polyethylene glycol-modified single-walled carbon nanotubes: potential implications on biological performance. ACS Nano 7(3), 1974-1989 (2013).
165. Yamada K, Yoshii S, Kumagai S, et al. High-density and highly surface selective adsorption of protein-nanoparticle complexes by controlling electrostatic interaction. Jpn J. Appl. Phys. 45(5R), 4259 (2006).
166. Cheng Z, Al Zaki A, Hui JZ, Muzykantov VR, Tsourkas A. Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science 338(6109), 903-910 (2012).
167. Tasciotti E, Liu X, Bhavane R, et al. Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat. Nanotechnol. 3(3), 151-157 (2008).
168. Shen H, Sun T, Ferrari M. Nanovector delivery of siRNA for cancer therapy. Cancer Gene Ther. 19(6), 367-373 (2012).
169. Blanco E, Ferrari M. Emerging nanotherapeutic strategies in breast cancer. Breast 23(1), 10-18 (2014).
170. Torchilin V. Intracellular delivery of protein and peptide therapeutics. Drug Discov. Today Technol. 5(2), e95-e103 (2008).
171. Parodi A, Quattrocchi N, Van De Ven AL, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat. Nanotechnol. 8(1), 61-68 (2013).
172. Corbo C, Parodi A, Evangelopoulos M, et al. Proteomic profiling of a biomimetic drug delivery platform. Curr. Drug Targets (2014) (Epub ahead of print).
173. Parodi A, Quattrocchi N, Van De Ven AL, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat. Nanotechnol. 8(1), 61-68 (2013).
174. Parodi A, Haddix SG, Taghipour N, et al. Bromelain surface modification increases the diffusion of silica nanopartides in the tumor extracellular matrix. ACS Nano 8(10), 9874-9883 (2014).
175. Albini A, Mussi V, Parodi A, et al. Interactions of single-wall carbon nanotubes with endothelial cells. Nanomedicine 6(2), 277-288 (2010).
176. Akita H, Kudo A, Minoura A, et al. Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process. Biomaterials 30(15), 2940-2949 (2009).
177. Hatakeyama H, Akita H, Harashima H. A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv. Drug Deliv. Rev. 63(3), 152-160 (2011).
178. Shaheen SM, Akita H, Nakamura T, et al. KALA-modified multi-layered nanoparticles as gene carriers for MHC class-I mediated antigen presentation for a DNA vaccine. Biomaterials 32(26), 6342-6350 (2011).