Recent in vivo evidences of particle-based delivery of small-interfering RNA (siRNA) into solid tumors

Journal of Pharmaceutical Innovation

Volumn 9, Issue 2, 2014, Pages 158-173

  Wen, Yi ^a   Meng, Wilson S ^a  

^a DUQUESNE UNIVERSITY   (United States)

Author keywords

Cell uptake; Endosome escape; Gene silencing; Inorganic nanoparticles; Liposomes; Polymeric nanoparticles; siRNA delivery; Tumor accumulation and penetration

Indexed keywords

CALCIUM PHOSPHATE; CARBON NANOTUBE; CHITOSAN; CYCLODEXTRIN; GOLD NANOPARTICLE; OLIGOPEPTIDE; POLYAMIDOAMINE; POLYETHYLENEIMINE; POLYMER; PROTEIN; SMALL INTERFERING RNA;

CELL MEMBRANE; ENDOSOME; GENE DELIVERY SYSTEM; GENE TARGETING; HUMAN; LIPOSOMAL GENE DELIVERY SYSTEM; POLYMERIZATION; PRIORITY JOURNAL; REVIEW; SOLID TUMOR; SYSTEMIC CIRCULATION;

EID: 84905757287     PISSN: 18725120     EISSN: 19398042     Source Type: Journal    
DOI: 10.1007/s12247-014-9183-4     Document Type: Review

References (177)

1. Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature. 2004;431:343-9. (Pubitemid 39265674)
2. Hannon GJ. RNA interference. Nature. 2002;418:244-51. (Pubitemid 34773784)
3. Rana TM. Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol. 2007;8(1):23-36. doi:10.1038/nrm2085. (Pubitemid 46012012)
4. Jinek M, Doudna JA. A three-dimensional view of the molecular machinery of RNA interference. Nature. 2009;457(7228):405-12. doi:10.1038/nature07755.
5. Fire A, Xu S, MMK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806-11. (Pubitemid 28099681)
6. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494-8. (Pubitemid 32494397)
7. McCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA. RNA interference in adult mice. Nature. 2002;418:38-9. (Pubitemid 34742563)
8. Hannon GJ, Rossi JJ. Unlocking the potential of the human genome with RNA interference. Nature. 2004;431:371-7.
9. Bumcrot D, Manoharan M, Koteliansky V, Sah DWY. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol. 2006;2(12):711-9. doi:10.1038/nchembio839. (Pubitemid 44764213)
10. Raemdonck K, Vandenbroucke RE, Demeester J, Sanders NN, De Smedt SC. Maintaining the silence: reflections on long-term RNAi. Drug Discov Today. 2008;13(21-22):917-31. doi:10.1016/j.drudis.2008.06.008.
11. Aagaard L, Rossi JJ. RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev. 2007;59(2-3):75-86. doi:10.1016/j.addr.2007.03. 005. (Pubitemid 46770900)
12. Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nat Rev Genet. 2007;8(3):173-84. doi:10.1038/nrg2006.
13. Khan AA, Betel D, Miller ML, Sander C, Leslie CS, Marks DS. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs. Nat Biotechnol. 2009;27(6):549-55. doi:10.1038/nbt.1543.
14. Jackson AL, Linsley PS. Recognizing and avoiding siRNA offtarget effects for target identification and therapeutic application. Nat Rev Drug Discov. 2010;9(1):57-67. doi:10.1038/nrd3010.
15. Sioud M. Innate sensing of self and non-self RNAs by Toll-like receptors. Trends Mol Med. 2006;12(4):167-76. doi:10.1016/j.molmed.2006.02.004.
16. Sledz CA, Holko M, de Veer MJ, Silverman RH, Williams BRG. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol. 2003;5(9):834-9. doi:10.1038/ncb1038. (Pubitemid 37087172)
17. Corey DR. Chemical modification: the key to clinical application of RNA interference? J Clin Invest. 2007;117(12):3615-22. doi:10.1172/jci33483. (Pubitemid 350224067)
18. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009;8(2):129-38. doi:10.1038/nrd2742.
19. Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature. 2004;432:173-8. (Pubitemid 39545841)
20. Zimmermann TS, Lee ACH, Akinc A, Bramlage B, Bumcrot D, Fedoruk MN, et al. RNAi-mediated gene silencing in non-human primates. Nature. 2006;441(7089):111-4. doi:10.1038/nature04688.
21. Pai SI, Lin YY, Macaes B, Meneshian A, Hung CF, Wu TC. Prospects of RNA interference therapy for cancer. Gene Ther. 2005;13(6):464-77. doi:10.1038/sj.gt.3302694.
22. de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov. 2007;6(6):443-53. (Pubitemid 47064567)
23. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145-60. doi:10.1038/nrd1632. (Pubitemid 40282557)
24. Ferrari M. Frontiers in cancer nanomedicine: directing mass transport through biological barriers. Trends Biotechnol. 2010;28(4):181-8. doi:10.1016/j.tibtech.2009.12.007.
25. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46:6387-92. (Pubitemid 17221789)
26. Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7(9):771-82. doi:10.1038/nrd2614.
27. Dobrovolskaia MA, Aggareal P, Hall JB, Mcneil SE. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol Pharm. 2008;5(4):487-95.
28. Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990;268(1):235-7. (Pubitemid 20233874)
29. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5(4):505-15.
30. Schroeder A, Levins CG, Cortez C, Langer R, Anderson DG. Lipid-based nanotherapeutics for siRNA delivery. J Intern Med. 2010;267(1):9-21. doi:10.1111/j.1365-2796.2009.02189.x.
31. Burke RS, Pun SH. Extracellular barriers to in vivo PEI and PEGylated PEI polyplex-mediated gene delivery to the liver. Bioconjug Chem. 2008;19:693-704. (Pubitemid 351431402)
32. Khalil IA. Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol Rev. 2006;58(1):32-45. doi:10.1124/pr.58.1.8.
33. Dominska M, Dykxhoorn DM. Breaking down the barriers: siRNA delivery and endosome escape. J Cell Sci. 2010;123(8):1183-9. doi:10.1242/jcs.066399.
34. Xu Y, Szoka Jr FC. Mechanism of DNA release from cationic liposome-DNA complexes used in cell transfection. Biochemistry (Mosc). 1996;35:5616-23. (Pubitemid 26143656)
35. Hafez IM, Maurer N, Cullis PR. On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther. 2001;8:1188-96. (Pubitemid 32776393)
36. Akinc A, Thomas M, Klibanov AM, Langer R. Exploring polyethylenimine- mediated DNA transfection and the proton sponge hypothesis. J Gene Med. 2005;7(5):657-63. doi:10.1002/jgm.696. (Pubitemid 40744532)
37. Sonawane ND. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J Biol Chem. 2003;278(45):44826-31. doi:10.1074/jbc.M308643200. (Pubitemid 37377241)
38. Stagmann T. Membrane fusion mechanisms the influenza hemagglutinin paradigm and its implications for intracellular fusion. Traffic. 2000;1:598-604.
39. Pinnaduwage P, Schmitt L, Huang L. Use of a quaternary ammonium detergent in liposome mediated DNA transfection of mouse L-cells. Biochim Biophys Acta. 1989;985(1):33-7. (Pubitemid 19240332)
40. Wang CY, Huang L. Highly efficient DNA delivery mediated by pH-sensitive immunoliposomes. Biochemistry (Mosc). 1989;28(24):9508-14. (Pubitemid 20000730)
41. Li S-D, Chen Y-C, Hackett MJ, Huang L. Tumor-targeted delivery of siRNA by self-assembled nanoparticles. Mol Ther. 2008;16(1):163-9. doi:10.1038/sj.mt.6300323.
42. Li S-D, Huang L. Nanoparticles evading the reticuloendothelial system: Role of the supported bilayer. Biochim Biophys Acta Biomembr. 2009;1788(10):2259-66. doi:10.1016/j.bbamem.2009.06.022.
43. Chono S, Li S-D, Conwell CC, Huang L. An efficient and low immunostimulatory nanoparticle formulation for systemic siRNA delivery to the tumor. J Control Release. 2008;131(1):64-9. doi:10.1016/j.jconrel.2008.07.006.
44. Wang Y, Xu Z, Guo S, Zhang L, Sharma A, Robertson GP, et al. Intravenous delivery of siRNA targeting CD47 effectively inhibits melanoma tumor growth and lung metastasis. Mol Ther. 2013;21(10):1919-29. doi:10.1038/mt.2013.135.
45. Wang Y, Zhang L, Guo S, Hatefi A, Huang L. Incorporation of histone derived recombinant protein for enhanced disassembly of core-membrane structured liposomal nanoparticles for efficient siRNA delivery. J Control Release. 2013;172(1):179-89. doi:10.1016/j.jconrel.2013.08.015.
46. Zhang Y, Peng L, Mumper RJ, Huang L. Combinational delivery of c-myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy. Biomaterials. 2013;34(33):8459-68. doi:10.1016/j.biomaterials. 2013.07.050.
47. Li J, Yang Y, Huang L. Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor. J Control Release. 2012;158(1):108-14. doi:10.1016/j.jconrel.2011.10.020.
48. Santel A, Aleku M, Endruschat J. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther. 2006;13:1222-34. (Pubitemid 44184716)
49. Aleku M, Schulz P, Keil O, Santel A, Schaeper U, Dieckhoff B, et al. Atu027, a Liposomal Small Interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res. 2008;68(23):9788-98. doi:10.1158/0008-5472.can-08-2428.
50. Pirollo KF, Rait A, Zhou Q, Hwang SH, Dagata JA, Zon G, et al. Materializing the potential of small-interfering RNA via a tumor-targeting nanodelivery system. Cancer Res. 2007;67(7):2938-43. doi:10.1158/0008-5472.can- 06-4535. (Pubitemid 46724828)
51. Yu W, Pirollo KF, Yu B, Rait A, Xiang L, Huang W, et al. Enhanced transfection efficiency of a systemically delivered tumor-targeting immunolipoplex by inclusion of a pH-sensitive histidylated oligolysine peptide. Nucleic Acids Res. 2004;32(5):e48.
52. Sato Y, Hatakeyama H, Sakurai Y, Hyodo M, Akita H, Harashima H. A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo. J Control Release. 2012;163(3):267-76. doi:10.1016/j.jconrel.2012.09.009.
53. Sakurai Y, Hatakeyama H, Sato Y, Hyodo M, Akita H, Harashima H. Gene silencing via RNAi and siRNA quantification in tumor tissue using MEND, a liposomal siRNA delivery system. Mol Ther. 2013;21(6):1195-203. doi:10.1038/mt.2013.57.
54. Sonoke S, Ueda T, Fujiwara K, Sato Y, Takagaki K, Hirabayashi K, et al. Tumor regression in mice by delivery of Bcl-2 small interfering RNA with pegylated cationic liposomes. Cancer Res. 2008;68(21):8843-51. doi:10.1158/0008-5472.can-08-0127.
55. Li L, Wang R, Wilcox D, Sarthy A, Lin X, Huang X, et al. Developing lipid nanoparticle-based siRNA therapeutics for hepatocellular carcinoma using an integrated approach. Mol Cancer Ther. 2013;12(11):2308-18. doi:10.1158/1535- 7163.mct-12-0983-t.
56. Tseng Y-C, Mozumdar S, Huang L. Lipid-based systemic delivery of siRNA. Adv Drug Deliv Rev. 2009;61(9):721-31. doi:10.1016/j.addr.2009.03.003.
57. Auguste D, Furman K, Wong A, Fuller J, Armes S, Deming T, et al. Triggered release of siRNA from poly(ethylene glycol)-protected, pH-dependent liposomes. J Control Release. 2008;130(3):266-74. doi:10.1016/j.jconrel.2008.06. 004.
58. Koren E, Apte A, Jani A, Torchilin VP. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J Control Release. 2012;160(2):264-73. doi:10.1016/j.jconrel.2011.12.002.
59. Lu JJ, Langer R, Chen J. A novel mechanism is involved in cationic lipid-mediated functional siRNA delivery. Mol Pharm. 2009;6(3):763-71.
60. Sahay G, Querbes W, Alabi C, Eltoukhy A, Sarkar S, Zurenko C, et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat Biotechnol. 2013;31(7):653-8. doi:10.1038/nbt.2614.
61. Gilleron J, Querbes W, Zeigerer A, Borodovsky A, Marsico G, Schubert U, et al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat Biotechnol. 2013;31(7):638-46. doi:10.1038/nbt.2612.
62. Zhang J, Liu F, Huang L. Implications of pharmacokinetic behavior of lipoplex for its inflammatory toxicity. Adv Drug Deliv Rev. 2005;57(5):689-98. doi:10.1016/j.addr.2004.12.004. (Pubitemid 40332597)
63. Dokka S, Toledo D, Shi X, Castranova V, Rojanasakul Y. Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes. Pharm Res. 2000;17(5):521-5. (Pubitemid 30416388)
64. Ma Z, Li J, He F, Wilson A, Pitt B, Li S. Cationic lipids enhance siRNA-mediated interferon response in mice. Biochem Biophys Res Commun. 2005;330(3):755-9. doi:10.1016/j.bbrc.2005.03.041. (Pubitemid 40462151)
65. Chen Y, Sen JS, Bathula SR, Yang Q, Fittipaldi R, Huang L. Novel cationic lipid that delivers siRNA and enhances therapeutic effect in lung cancer cells. Mol Pharm. 2009;6(3):696-705.
66. Chen Y, Bathula SR, Yang Q, Huang L. Targeted nanoparticles deliver siRNA to melanoma. J Invest Dermatol. 2010;130(12):2790-8. doi:10.1038/jid.2010.222.
67. Landen CN. Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 2005;65(15):6910-8. doi:10.1158/0008-5472.can-05-0530.
68. Halder J. Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin Cancer Res. 2006;12(16):4916-24. doi:10.1158/1078-0432.ccr-06-0021. (Pubitemid 44338579)
69. Mangala LS, Zuzel V, Schmandt R, Leshane ES, Halder JB, Armaiz-Pena GN, et al. Therapeutic targeting of ATP7B in ovarian carcinoma. Clin Cancer Res. 2009;15(11):3770-80. doi:10.1158/1078-0432.ccr-08-2306.
70. Merritt WM, Lin YG, Spannuth WA, Fletcher MS, Kamat AA, Han LY, et al. Effect of interleukin-8 gene silencing with liposomeencapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst. 2008;100(5):359-72. doi:10.1093/jnci/djn024. (Pubitemid 351480526)
71. Vivas-Mejia PE, Rodriguez-Aguayo C, Han HD, Shahzad MMK, Valiyeva F, Shibayama M, et al. Silencing survivin splice variant 2B leads to antitumor activity in taxane-resistant ovarian cancer. Clin Cancer Res. 2011;17(11):3716-26. doi:10.1158/1078-0432.ccr-11-0233.
72. Chakravarty D, Roy SS, Babu CR, Dandamudi R, Curiel TJ, Vivas-Mejia P, et al. Therapeutic targeting of PELP1 prevents ovarian cancer growth and metastasis. Clin Cancer Res. 2011;17(8):2250-9. doi:10.1158/1078-0432.ccr-10- 2718.
73. Gray MJ, Dallas NA, Van Buren G, Xia L, Yang AD, Somcio RJ, et al. Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver. Oncogene. 2008;27(57):7192-200. doi:10.1038/onc.2008.356.
74. Gray MJ, Van Buren G, Dallas NA, Xia L, Wang X, Yang AD, et al. Therapeutic targeting of neuropilin-2 on colorectal carcinoma cells implanted in the murine liver. J Natl Cancer Inst. 2008;100(2):109-20. doi:10.1093/jnci/ djm279. (Pubitemid 351480563)
75. Villares GJ, Zigler M, Wang H, Melnikova VO, Wu H, Friedman R, et al. Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA. Cancer Res. 2008;68(21):9078-86. doi:10.1158/0008-5472.can-08-2397.
76. Miller CR, Bondurant B, McLean SD, McGovern KA, O'Brien DF. Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry (Mosc). 1998;37(37):12875-83. (Pubitemid 28433520)
77. Kostarelos K, Emfietzoglou D, Papakostas A, Yang W-H, Ballangrud Å, Sgouros G. Binding and interstitial penetration of liposomes within avascular tumor spheroids. Int J Cancer. 2004;112(4):713-21. doi:10.1002/ijc.20457. (Pubitemid 39425955)
78. Tanaka T, Mangala LS, Vivas-Mejia PE, Nieves-Alicea R, Mann AP, Mora E, et al. Sustained small interfering RNA delivery by mesoporous silicon particles. Cancer Res. 2010;70(9):3687-96. doi:10.1158/0008-5472.can-09-3931.
79. Jin J, Bae KH, Yang H, Lee SJ, Kim H, Kim Y, et al. In vivo specific delivery of c-Met siRNA to glioblastoma using cationic solid lipid nanoparticles. Bioconjug Chem. 2011;22(12):2568-72. doi:10.1021/bc200406n.
80. Shahzad MMK, Mangala LS, Han HD, Lu C, Bottsford-Miller J, Nishimura M, et al. Targeted delivery of small interfering RNA using reconstituted high density lipoprotein nanoparticles. Neoplasia. 2011;13(4):309-19. doi:10.1593/neo.101372.
81. Wolfrum C, Shi S, Jayaprakash KN, Jayaraman M, Wang G, Pandey RK, et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol. 2007;25(10):1149-57. doi:10.1038/nbt1339. (Pubitemid 47538115)
82. Tomlinson E, Rolland AP. Controllable gene therapy pharmaceutics of non-viral gene delivery systems. J Control Release. 1996;39(2-3):357-72. (Pubitemid 26194229)
83. Howard KA. Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev. 2009;61(9):710-20. doi:10.1016/j.addr.2009.04.001.
84. Bartlett DW, Davis ME. Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjug Chem. 2007;18:456-68. (Pubitemid 46493517)
85. Davis ME, Zuckerman JE, Choi CHJ, Seligson D, Tolcher A, Alabi CA, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010;464(7291):1067-70. doi:10.1038/nature08956.
86. Hwang SH, Bellocq NC, Davis ME. Effects of structure of beta-cyclodextrin-containing polymers on gene delivery. Bioconjug Chem. 2001;12:280-90. (Pubitemid 32235481)
87. Reineke TM, Davis ME. Structural effects of carbohydrate-containing polycations on gene delivery. 1. Carbohydrate size and its distance from charge centers. Bioconjug Chem. 2003;14(247-254). (Pubitemid 36169039)
88. Reineke TM, Davis ME. Structural effects of carbohydratecontaining polycations on gene delivery. 2. Charge center type. Bioconjug Chem. 2003;14:255-61. (Pubitemid 36169040)
89. Popielarski SR, Mishra S, Davis ME. Structural effects of carbohydrate-containing polycations on gene delivery. 3. Cyclodextrin type and functionalization. Bioconjug Chem. 2003;14:672-8. (Pubitemid 36597379)
90. Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci U S A. 2007;104(39):15549-54. doi:10.1073/pnas.0707461104. (Pubitemid 47502954)
91. Bartlett DW, Davis ME. Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles. Biotechnol Bioeng. 2008;99(4):975-85. doi:10.1002/bit.21668. (Pubitemid 351316639)
92. Günther M, Lipka J, Malek A, Gutsch D, Kreyling W, Aigner A. Polyethylenimines for RNAi-mediated gene targeting in vivo and siRNA delivery to the lung. Eur J Pharm Biopharm. 2011;77(3):438-49. doi:10.1016/j.ejpb.2010.11. 007.
93. Neu M, Fischer D, Kissel T. Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. J Gene Med. 2005;7(8):992-1009. doi:10.1002/jgm.773. (Pubitemid 41195062)
94. Rejman J, Bragonzi A, Conese M. Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes. Mol Ther. 2005;12(3):468-74. doi:10.1016/j.ymthe.2005.03.038. (Pubitemid 41150132)
95. Hunter A. Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity. Adv Drug Deliv Rev. 2006;58(14):1523-31. doi:10.1016/j.addr.2006.09.008. (Pubitemid 44820504)
96. Vongersdorff K, Sanders N, Vandenbroucke R, Desmedt S, Wagner E, Ogris M. The internalization route resulting in successful gene expression depends on both cell line and polyethylenimine polyplex type. Mol Ther. 2006;14(5):745-53. doi:10.1016/j.ymthe.2006.07.006. (Pubitemid 44480760)
97. Godbey WT, Wu KK, Mikos AG. Size matters: molecular weight affects the efficiency of poly(ethylenimine) as a gene delivery vehicle. Biochim Biophys Acta Gen Subj. 1999;1725(3):377-84.
98. Werth S, Urban-Klein B, Dai L, Höbel S, Grzelinski M, Bakowsky U, et al. A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes. J Control Release. 2006;112(2):257-70. doi:10.1016/j.jconrel.2006.02. 009.
99. Hobel S, Koburger I, John M, Czubayko F, Hadwiger P, Vornlocher H-P, et al. Polyethylenimine/small interfering RNA-mediated knockdown of vascular endothelial growth factorin vivoexerts anti-tumor effects synergistically with Bevacizumab. J Gene Med. 2010;12:287-300. doi:10.1002/jgm.1431.
100. Hendruschk S, Wiedemuth R, Aigner A, Topfer K, Cartellieri M, Martin D, et al. RNA interference targeting survivin exerts antitumoral effects in vitro and in established glioma xenografts in vivo. Neuro-oncol. 2011;13(10):1074-89. doi:10.1093/neuonc/nor098.
101. Kaestner P, Aigner A, Bastians H. Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo. Cancer Lett. 2011;304(2):128-36. doi:10.1016/j.canlet.2011.02. 014.
102. Thomas M. Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells. Proc Natl Acad Sci U S A. 2002;99(23):14640-5. doi:10.1073/pnas.192581499. (Pubitemid 35334537)
103. Tarcha PJ, Pelisek J, Merdan T, Waters J, Cheung K, von Gersdorff K, et al. Synthesis and characterization of chemically condensed oligoethylenimine containing beta-aminopropionamide linkages for siRNA delivery. Biomaterials. 2007;28(25):3731-40. doi:10.1016/j.biomaterials.2007.04.037. (Pubitemid 46855884)
104. Breunig M, Lungwitz U, Liebl R, Goepferich A. Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. Proc Natl Acad Sci U S A. 2007;104(36):14454-9. doi:10.1073/pnas.0703882104. (Pubitemid 350003282)
105. Breunig M, Hozsa C, Lungwitz U, Watanabe K, Umeda I, Kato H, et al. Mechanistic investigation of poly(ethylene imine)-based siRNA delivery: Disulfide bonds boost intracellular release of the cargo. J Control Release. 2008;130(1):57-63. doi:10.1016/j.jconrel.2008.05.016.
106. Jiang G, Park K, Kim J, Kim KS, Hahn SK. Target specific intracellular delivery of siRNA-PEI - HA complex by receptor mediated endocytosis. Mol Pharm. 2009;6(3):727-37.
107. Ganesh S, Iyer AK, Morrissey DV, Amiji MM. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors. Biomaterials. 2013;34(13):3489-502.
108. Höbel S, Loos A, Appelhans D, Schwarz S, Seidel J, Voit B, et al. Maltose- and maltotriose-modified, hyperbranched poly(ethylene imine)s (OM-PEIs): physicochemical and biological properties of DNA and siRNA complexes. J Control Release. 2011;149(2):146-58. doi:10.1016/j.jconrel.2010.10.008.
109. Zintchenko A, Philipp A, Dehshahri A, Wagner E. Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. Bioconjug Chem. 2008;19:1448-55. (Pubitemid 352032345)
110. Schroeder A, Dahlman JE, Sahay G, Love KT, Jiang S, Eltoukhy AA, et al. Alkane-modified short polyethyleneimine for siRNA delivery. J Control Release. 2012;160(2):172-6. doi:10.1016/j.jconrel.2011.11.030.
111. Navarro G, Sawant RR, Biswas S, Conchita SE, Ilarduya T, Torchilin VP. P-glycoprotein silencing with siRNA delivered by DOPE-modified PEI overcomes doxorubicin resistance in breast cancer cells. Nanomedicine. 2012;7(1):65-78.
112. Alshamsan A, Hamdy S, Samuel J, El-Kadi AOS, Lavasanifar A, Uludaǧ H. The induction of tumor apoptosis in B16 melanoma following STAT3 siRNA delivery with a lipid-substituted polyethylenimine. Biomaterials. 2010;31(6):1420-8. doi:10.1016/j.biomaterials.2009.11.003.
113. Kim WJ, Chang C-W, Lee M, Kim SW. Efficient siRNA delivery using water soluble lipopolymer for anti-angiogenic gene therapy. J Control Release. 2007;118(3):357-63. doi:10.1016/j.jconrel.2006.12.026. (Pubitemid 46441547)
114. Malek A, Merkel O, Fink L, Czubayko F, Kissel T, Aigner A. In vivo pharmacokinetics, tissue distribution and underlying mechanisms of various PEI (- PEG)/siRNA complexes. Toxicol Appl Pharmacol. 2009;236(1):97-108. doi:10.1016/j.taap.2009.01.014.
115. Kim J, Kim SW, Kim WJ. PEI-g-PEG-RGD/small interference RNA polyplex-mediated silencing of vascular endothelial growth factor receptor and its potential as an anti-angiogenic tumor therapeutic strategy. Oligonucleotides. 2011;21(2):101-7. doi:10.1089/oli.2011.0278.
116. Schiffelers RM. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res. 2004;32(19):e149. doi:10.1093/nar/gnh140.
117. Zheng M, Librizzi D, Kiliç A, Liu Y, Renz H, Merkel OM, et al. Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) copolymers. Biomaterials. 2012;33(27):6551-8. doi:10.1016/j.biomaterials.2012.05.055.
118. Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. Local and systemic delivery of VEGF siRNA using polyelectrolyte complex micelles for effective treatment of cancer. J Control Release. 2008;129(2):107-16. doi:10.1016/j.jconrel.2008.03. 008.
119. Shim MS, Chang S-S, Kwon YJ. Stimuli-responsive siRNA carriers for efficient gene silencing in tumors via systemic delivery. Biomater Sci. 2014;2(1):35. doi:10.1039/c3bm60187k.
120. Zhu L, Perche F, Wang T, Torchilin VP. Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific codelivery of siRNA and hydrophobic drugs. Biomaterials. 2014;35(13):4213-22. doi:10.1016/j.biomaterials.2014.01.060.
121. Boeckle S, von Gersdorff K, van der Piepen S, Culmsee C, Wagner E, Ogris M. Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer. J Gene Med. 2004;6(10):1102-11. doi:10.1002/jgm.598. (Pubitemid 40228122)
122. Freeman E, Weiland LM, Meng WS. Application of proteins in burst delivery systems. Smart Mater Struct. 2010;19(9):094015. doi:10.1088/0964-1726/19/9/ 094015.
123. Freeman E, Weiland LM, Meng WS. Modeling the proton sponge hypothesis: examining proton sponge effectiveness for enhancing intracellular gene delivery through multiscale modeling. J Biomater Sci Polym Ed. 2013;24(4):398-416.
124. Pavan GM, Albertazzi L, Danani A. Ability to adapt- different generations of PAMAM dendrimers show different behaviors in binding siRNA. J Phys Chem B. 2010;114:2667-75.
125. Posocco P, Liu X, Laurini E, Marson D, Chen C, Liu C, et al. Impact of siRNA overhangs for dendrimer-mediated siRNA delivery and gene silencing. Mol Pharm. 2013;10(8):3262-73. doi:10.1021/mp400329g.
126. Liu X, Liu C, Laurini E, Posocco P, Pricl S, Qu F, et al. Efficient delivery of sticky siRNA and potent gene silencing in a prostate cancer model using a generation 5 triethanolamine-core PAMAM dendrimer. Mol Pharm. 2012;9(3):470-81. doi:10.1021/mp2006104.
127. Yu T, Liu X, Bolcato-Bellemin A-L, Wang Y, Liu C, Erbacher P, et al. An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo. Angew Chem Int Ed. 2012;51(34):8478-84. doi:10.1002/anie.201203920.
128. Patil ML, Zhang M, Taratula O, Garbuzenko OB, He H, Minko T. Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery- effect of the degree of quaternization and cancer targeting. Biomacromolecules. 2009;10:258-66.
129. Chen C-J, Wang J-C, Zhao E-Y, Gao L-Y, Feng Q, Liu X-Y, et al. Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery. Biomaterials. 2013;34(21):5303-16. doi:10.1016/j.biomaterials.2013.03.056.
130. Lin D, Jiang Q, Cheng Q, Huang Y, Huang P, Han S, et al. Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery. Acta Biomater. 2013;9(8):7746-57. doi:10.1016/j.actbio.2013.04.031.
131. Tanaka K, Kanazawa T, Horiuchi S, Ando T, Sugawara K, Takashima Y, et al. Cytoplasm-responsive nanocarriers conjugated with a functional cell-penetrating peptide for systemic siRNA delivery. Int J Pharm. 2013;455(1-2):40-7. doi:10.1016/j.ijpharm.2013.07.069.
132. Borchard G. Chitosans for gene delivery. Adv Drug Deliv Rev. 2001;52:145-50. (Pubitemid 33079170)
133. Liu X, Howard KA, Dong M, Andersen MØ, Rahbek UL, Johnsen MG, et al. The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. Biomaterials. 2007;28(6):1280-8. doi:10.1016/j.biomaterials.2006.11.004. (Pubitemid 44816373)
134. Han HD, Mangala LS, Lee JW, Shahzad MMK, Kim HS, Shen D, et al. Targeted gene silencing using RGD-labeled chitosan nanoparticles. Clin Cancer Res. 2010;16(15):3910-22. doi:10.1158/1078-0432.ccr-10-0005.
135. Pille J, Li H, Blot E, Bertrand J, Pritchard L, Opolon P, et al. Intravenous delivery of anti-RhoA small interfering RNA loaded in nanoparticles of chitosan in mice safety and efficacy in xenografted aggressive breast cancer. Hum Gene Ther. 2006;17:1019-26. (Pubitemid 46076743)
136. de Martimprey H, Bertrand JR, Fusco A, Santoro M, Couvreur P, Vauthier C et al. siRNA nanoformulation against the Ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma. Nucleic Acids Res. 2007;36(1):e2. doi:10.1093/nar/gkm1094.
137. Yang F, Huang W, Li Y, Liu S, Jin M, Wang Y, et al. Anti-tumor effects in mice induced by survivin-targeted siRNA delivered through polysaccharide nanoparticles. Biomaterials. 2013;34(22):5689-99. doi:10.1016/j.biomaterials. 2013.03.047.
138. Son S, Song S, Lee SJ, Min S, Kim SA, Yhee JY, et al. Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors. Biomaterials. 2013;34(37):9475-85. doi:10.1016/j.biomaterials.2013.08. 085.
139. Yhee JY, Lee SJ, Lee S, Song S, Min HS, Kang S-W, et al. Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice. Bioconjug Chem. 2013;24(11):1850-60. doi:10.1021/bc400226b.
140. Kawata E, Ashihara E, Kimura S, Takenaka K, Sato K, Tanaka R, et al. Administration of PLK-1 small interfering RNA with atelocollagen prevents the growth of liver metastases of lung cancer. Mol Cancer Ther. 2008;7(9):2904-12. doi:10.1158/1535-7163.mct-08-0473.
141. Adachi T, Kawakami E, Ishimaru N, Ochiya T, Hayashi Y, Ohuchi H, et al. Delivery of small interfering RNAwith a synthetic collagen poly(Pro-Hyp-Gly) for gene silencing in vitro and in vivo. Dev Growth Differ. 2010;52(8):693-9. doi:10.1111/j.1440-169X.2010.01206.x.
142. Kim SW, Kim NY, Choi YB, Park SH, Yang JM, Shin S. RNA interference in vitro and in vivo using an arginine peptide/siRNA complex system. J Control Release. 2010;143(3):335-43. doi:10. 1016/j.jconrel.2010.01.009.
143. Kim W, Christensen L, Jo S, Yockman J, Jeong J, Kim Y, et al. Cholesteryl oligoarginine delivering vascular endothelial growth factor siRNA effectively inhibits tumor growth in colon adenocarcinoma. mol ther. 2006;14(3):343-50. doi:10.1016/j.ymthe.2006.03.022.
144. Crombez L, Morris MC, Dufort S, Aldrian-Herrada G, Nguyen Q, Mc Master G, et al. Targeting cyclin B1 through peptide-based delivery of siRNA prevents tumour growth. Nucleic Acids Res. 2009;37(14):4559-69. doi:10.1093/nar/gkp451.
145. Lee SJ, Yhee JY, Kim SH, Kwon IC, Kim K. Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice. J Control Release. 2013;172(1):358-66. doi:10.1016/j.jconrel.2013.09.002.
146. Minakuchi Y. Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. Nucleic Acids Res. 2004;32(13):e109. doi:10.1093/nar/gnh093.
147. Beloor J, Choi CS, Nam HY, Park M, Kim SH, Jackson A, et al. Arginine-engrafted biodegradable polymer for the systemic delivery of therapeutic siRNA. Biomaterials. 2012;33(5):1640-50. doi:10.1016/j.biomaterials. 2011.11.008.
148. Wang Z, Liu G, Zheng H, Chen X. Rigid nanoparticle-based delivery of anti-cancer siRNA: challenges and opportunities. Biotech Adv. 2013. doi:10.1016/j.biotechadv.2013.08.020.
149. Lytton-Jean AKR, Langer R, Anderson DG. Five years of siRNA delivery: spotlight on gold nanoparticles. Small. 2011;7(14):1932-7. doi:10.1002/smll. 201100761.
150. Patel PC, Giljohann DA, Daniel WL, Zheng D, Prigodich AE, Mirkin CA. Scavenger receptors mediate cellular uptake of polyvalent oligonucleotide- functionalized gold nanoparticles. Bioconjug Chem. 2010;21:2250-6.
151. Conde J, Tian F, Hernández Y, Bao C, Cui D, Janssen K-P, et al. In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models. Biomaterials. 2013;34(31):7744-53. doi:10.1016/j.biomaterials.2013.06.041.
152. Lu W, Zhang G, Zhang R, Flores LG, Huang Q, Gelovani JG, et al. Tumor site-specific silencing of NF- B p65 by targeted hollow gold nanosphere-mediated photothermal transfection. Cancer Res. 2010;70(8):3177-88. doi:10.1158/0008- 5472.can-09-3379.
153. Elhissi AMA, Ahmed W, Hassan IU, Dhanak VR, D'Emanuele A. Carbon nanotubes in cancer therapy and drug delivery. J Drug Deliv. 2012;2012:1-10. doi:10.1155/2012/837327.
154. Podesta JE, Al-Jamal KT, Herrero MA, Tian B, Ali-Boucetta H, Hegde V, et al. Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model. Small. 2009;5(10):1176-85. doi:10.1002/smll.200801572.
155. Pittella F, Zhang M, Lee Y, Kim HJ, Tockary T, Osada K, et al. Enhanced endosomal escape of siRNA-incorporating hybrid nanoparticles from calcium phosphate and PEG-block charge-conversional polymer for efficient gene knockdown with negligible cytotoxicity. Biomaterials. 2011;32(11):3106-14. doi:10.1016/j.biomaterials.2010.12.057.
156. Pittella F, Cabral H, Maeda Y, Mi P, Watanabe S, Takemoto H, et al. Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic mice by PEGylated calcium phosphate hybrid micelles. J Control Release. 2014;178:18-24. doi:10.1016/j.jconrel.2014.01.008.
157. Jiang S, Eltoukhy AA, Love KT, Langer R, Anderson DG. Lipidoid-coated iron oxide nanoparticles for efficient DNA and siRNA delivery. Nano Lett. 2013;13(3):1059-64. doi:10.1021/nl304287a.
158. Li L, Gu W, Chen J, Chen W, Xu ZP. Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles. Biomaterials. 2014;35(10):3331-9. doi:10.1016/j.biomaterials.2013.12.095.
159. Chamarthy SP, Kovacs JR, McClelland E, Gattens D, Meng WS. A cationic peptide consists of ornithine and histidine repeats augments gene transfer in dendritic cells. Mol Immunol. 2003;40(8):483-90. doi:10.1016/j.molimm.2003.08. 001. (Pubitemid 37244024)
160. Kovacs JR, Zheng Y, Shen H, Meng WS. Polymeric microspheres as stabilizing anchors for oligonucleotide delivery to dendritic cells. Biomaterials. 2005;26(33):6754-61. doi:10.1016/j.biomaterials.2005.04.022. (Pubitemid 41021768)
161. Meng WS, Butterfield LH. Activation of antigen-presenting cells by DNA delivery vectors. Expert Opin Biol Ther. 2005;5(8):1019-28. (Pubitemid 41170032)
162. Pack DW, Hoffman AS, Pun S, Stayton PS. Design and development of polymers for gene delivery. Nat Rev Drug Discov. 2005;4(7):581-93. doi:10.1038/nrd1775. (Pubitemid 40975711)
163. Kullberg M, McCarthy R, Anchordoquy TJ. Systemic tumorspecific gene delivery. J Control Release. 2013;172(3):730-6. doi: 10.1016/j.jconrel.2013.08. 300.
164. Rojanasakul Y. Antisense oligonucleotide therapeutics drug delivery and targeting. Adv Drug Deliv Rev. 1996;18:115-31. (Pubitemid 26041540)
165. Rozema DB, Lewis DL, Wakefield DH, Wong SC, Klein JJ, Roesch PL, et al. Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc Natl Acad Sci U S A. 2007;104(32):12982-7. doi:10.1073/pnas.0703778104. (Pubitemid 351737577)
166. Wooddell CI, Rozema DB, Hossbach M, John M, Hamilton HL, Chu Q, et al. Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis B virus infection. Mol Ther. 2013;21(5):973-85. doi:10.1038/mt.2013.31.
167. Wong SC, Klein JJ, Hamilton HL, Chu Q, Frey CL, Trubetskoy VS, et al. Co-injection of a targeted, reversibly masked endosomolytic polymer dramatically improves the efficacy of cholesterol-conjugated small interfering RNAs in vivo. Nucleic Acid Ther. 2012;22(6):380-90.
168. Grodzinski P, Farrell D. Future opportunities in cancer nanotechnology - NCI strategic workshop report. Cancer Res. 2014;74(5): 1307-10.
169. Judge A, McClintock K, Phelps J, Maclachlan I. Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. Mol Ther. 2006;13(2):328-37. doi:10.1016/j.ymthe.2005.09.014. (Pubitemid 43056898)
170. Kim JS, Oh MH, Park JY, Park TG, Nam YS. Protein-resistant, reductively dissociable polyplexes for in vivo systemic delivery and tumor-targeting of siRNA. Biomaterials. 2013;34(9):2370-9. doi:10.1016/j.biomaterials.2012.12.004.
171. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58-62. doi:10.1126/science. 1104819. (Pubitemid 40093472)
172. Li L, Wang R, Wilcox D, Zhao X, Song J, Lin X, et al. Tumor vasculature is a key determinant for the efficiency of nanoparticle-mediated siRNA delivery. Gene Ther. 2011;19(7):775-80. doi:10.1038/gt.2011.146.
173. Semple SC, Akinc A, Chen J, Sandhu AP, Mui BL, Cho CK, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol. 2010;28(2):172-6. doi:10.1038/nbt.1602.
174. Zhang Y, Pelet JM, Heller DA, Dong Y, Chen D, Gu Z, et al. Lipid-modified aminoglycoside derivatives for in vivo siRNA delivery. Adv Mater. 2013;25(33):4641-5. doi:10.1002/adma.201301917.
175. Guk K, Lim H, Kim B, Hong M, Khang G, Lee D. Acid-cleavable ketal containing poly(β-amino ester) for enhanced siRNA delivery. Int J Pharm. 2013;453(2):541-50. doi:10.1016/j.ijpharm.2013.06.021.
176. Hong BJ, Chipre AJ, Nguyen ST. Acid-degradable polymer-caged lipoplex (PCL) platform for siRNA delivery: facile cellular triggered release of siRNA. J Am Chem Soc. 2013;135(47):17655-8. doi:10.1021/ja404491r.
177. Abeylath SC, Ganta S, Iyer AK, Amiji M. Combinatorial-designed multifunctional polymeric nanosystems for tumor-targeted therapeutic delivery. Acc Chem Res. 2011;44(10):1009-17.