Smart siRNA delivery systems based on polymeric nanoassemblies and nanoparticles

Nanomedicine

Volumn 5, Issue 7, 2010, Pages 1089-1102

  Tamura, Atsushi ^a   Nagasaki, Yukio ^a  

^a UNIVERSITY OF TSUKUBA   (Japan)

Author keywords

biopolymer; cationic polymer; nanogel; PEGylation; poly(ethylenimine); polyion complex; RNA interference; siRNA; stimulus sensitive polymer; synthetic polymer

Indexed keywords

BIOPOLYMER; CHITOSAN; MACROGOL; NANOPARTICLE; POLYCYSTAMINEBISACRYLAMIDE DIAMINOHEXANE; POLYETHYLENEIMINE; POLYMER; RIBONUCLEASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

CELL TRANSPORT; COMPLEX FORMATION; DRUG ACTIVITY; DRUG DELIVERY SYSTEM; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG FORMULATION; DRUG PENETRATION; DRUG RELEASE; DRUG SOLUBILITY; DRUG STABILITY; DRUG TARGETING; DRUG TOLERABILITY; ENZYME STABILITY; GENE SILENCING; INTERNALIZATION; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; STRUCTURE ACTIVITY RELATION;

ANIMALS; GENE SILENCING; HUMANS; MICE; NANOPARTICLES; POLYMERS; RNA, SMALL INTERFERING;

EID: 77957605164     PISSN: 17435889     EISSN: None     Source Type: Journal    
DOI: 10.2217/nnm.10.76     Document Type: Review

References (112)

1. Paterson BM, Roberts BE, Kuff EL: Structural gene identification and mapping by DNA-mRNA hybrid-arrested cell-free translation. Proc. Natl Acad. Sci. USA 74(10), 4370-4374 (1977).
2. Zamecnik PC, Stephenson ML: Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc. Natl Acad. Sci. USA 75(1), 280-284 (1978).
3. Stephenson ML, Zamecnik PC: Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc. Natl Acad. Sci. USA 75(1), 285-288 (1978).
4. Breaker RR: Natural and engineered nucleic acids as tools to explore biology. Nature 432(7019), 838-845 (2004).
5. Gewirtz AM, Sokol DL, Ratajczak MZ: Nucleic acid therapeutics: state of the art and future prospects. Blood 92(3), 712-736 (1988).
6. Stull RA, Szoka FC Jr: Antigene, ribozyme and aptamer nucleic acid drugs: progress and prospects. Pharm. Res. 12(4), 465-483 (1995).
7. Opalinska JB, Gewirtz AM: Nucleic-acid therapeutics: basic principles and recent applications. Nat. Rev. Drug Discov. 1(7), 503-514 (2002).
8. Gleave ME, Monia BP: Antisense therapy for cancer. Nat. Rev. Drug Discov. 5(6), 468-479 (2005).
9. Grillone LR, Lanz R: Formivirsen. Drugs Today 37(4), 245-255 (2001).
10. Ng EWM, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP: Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat. Rev. Drug Discov. 5(2), 123-132 (2006).
11. Dorsett Y, Tuschl T: siRNAs: Applications in functional genomics and potential as therapeutics. Nat. Rev. Drug Discov. 3(4), 318-329 (2004).
12. Iorns E, Lord CJ, Turner N, Ashworth A: Utilizing RNA interference to enhance cancer drug discovery. Nat. Rev. Drug Discov. 6(7), 556-568 (2007).
13. Bumcrot D, Manoharan M, Koteliansky V, Sah DWY: RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol. 2(12), 711-719 (2006).
14. Behlke MA: Progress towards in vivo use of siRNAs. Mol. Ther. 13(4), 644-670 (2006).
15. Kim DH, Rossi JJ: Strategies for silencing human disease using RNA interference. Nat. Rev. Genetics 8(3), 173-184 (2007).
16. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669), 806-811 (1998). (Pubitemid 28099681)
17. Zamore PD, Tuschl T, Sharp PA, Bartel DP: RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101(1), 25-33 (2000).
18. Elbashir SM, Lendeckel W, Tuschl T: RNA interference is mediated by 21-and 22-nucleotide RNAs. Genes Dev. 15(2), 188-200 (2001). (Pubitemid 32107664)
19. Stark GR, Kerr IM, Williams BRG, Silverman RH, Schreiber RD: How cells respond to interferons. Annu. Rev. Biochem. 67, 227-264 (1998).
20. 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 411(6836), 494-498 (2001).
21. Martinez J, Patkaniowska A, Urlaub H, Lührmann R, Tuschl T: Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 110(5), 563-574 (2002).
22. Whitehead KA, Langer R, Anderson DG: Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8(2), 129-138 (2009).
23. Manoharan M: RNA interference and chemically modified small interfering RNAs. Curr. Opin. Chem. Biol. 8(6), 570-579 (2004).
24. Zhang HY, Du Q, Wahlestedt C, Liang Z: RNA interference with chemically modified siRNA. Curr. Top. Med. Chem. 6(9), 893-900 (2006).
25. Jeong JH, Mok H, Oh YK, Park TG: siRNA conjugate delivery systems. Bioconjugate Chem. 20, 5-14 (2009).
26. Gao S, Dagnaes-Hansen F, Nielsen EJB et al.: The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol. Ther. 17(7), 1225-1233 (2009).
27. Braasch DA, Paroo Z, Constantinescu A et al.: Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorg. Med. Chem. Lett. 14(5), 1139-1143 (2004).
28. Kim WJ, Kim SW: Efficient siRNA delivery with nonviral polymeric vehicles. Pharm. Res. 26(3), 657-666 (2008).
29. Zhang S, Zhao B, Jiang H, Wang B, Ma B: Cationic lipids and polymers mediated vectors for delivery of siRNA. J. Controlled Release 123(1), 1-10 (2007).
30. Pack DW, Hoffman AS, Pun S, Stayton PS: Design and development of polymers for gene delivery. Nat. Rev. Drug Discov. 4(7), 581-593 (2005).
31. Bloomfield VA: DNA condensation by multivalent cations. Biopolymers 44(3), 269-282 (1997).
32. Boussif O, Lezoualc'h F, Zanta MA et al.: A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl Acad. Sci. USA 92(16), 7297-7301 (1995).
33. Behr JP: The proton sponge: A trick to enter cells the viruses did not exploit. Chimia 51(1-2), 34-36 (1997).
34. Sonawane ND, Szoka Jr. FC, Verkman AS: Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J. Biol. Chem. 278(45), 44826-44831 (2003).
35. Urban-Klein B, Werth S, Abuharbeid S, Czubayko F, Aigner A: RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther. 12(5), 461-466 (2005).
36. Esfand R, Tomalia DA: Poly (amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov. Today 6(8), 427-436 (2001).
37. Dufès C, Uchegbu IF, Schätzlein AG: Dendrimers in gene delivery. Adv. Drug Deliv. Rev. 57(15), 2177-2202 (2005).
38. Zhou J, Wu J, Hafdi N, Behr JP, Erbacher P, Peng L: PAMAM dendrimers for efficient siRNA delivery and potent gene silencing. Chem. Commun. 2362-2364 (2006).
39. Watanabe K, Harada-Shiba M, Suzuki A et al.: In vivo siRNA delivery with dendritic poly (L-lysine) for the treatment of hypercholesterolemia. Mol. BioSyst. 5(11), 1306-1310 (2009).
40. Taratula O, Garbuzenko OB, Kirkpatrick P et al.: Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery. J. Controlled Release 140(3), 284-293 (2009).
41. Mao S, Sun W, Kissel T: Chitosan-based formulations for delivery of DNA and siRNA. Adv. Drug Deliv. Rev. 62, 12-27 (2010).
42. Liu X, Howard KA, Dong M et al.: The influence of polymeric properties on chitosan-siRNA nanoparticle formulation and gene silencing. Biomaterials 28, 1280-1288 (2007).
43. Katas H, Alpar HO: Development and characterisation of chitosan nanoparticles for siRNA delivery. J. Controlled Release 115(2), 216-225 (2006).
44. Howard KA, Rahbek UL, Liu X et al.: RNA interference in vitro and in vivo using a chitosan-siRNA nanoparticle system. Mol. Ther. 14, 476-484 (2006).
45. Moghimi SM, Szebeni J: Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res. 42(6), 463-478 (2003).
46. Harris JM, Chess RB: Effect of PEGylation on pharmaceuticals. Nat. Rev. Drug Discov. 2(3), 214-221 (2003).
47. van Vlerken LE, Vyas TK, Amiji MM: Poly (ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm. Res. 24(8), 1405-1414 (2007).
48. Sato A, Choi SW, Hirai M et al.: Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life. J. Controlled Release 122(3), 209-216 (2007).
49. Scales CW, Huang F, Li N et al.: Coronastabilized interpolyelectrolyte complexes of siRNA with nonimmunogenic, hydrophilic/cationic block copolymers prepared by aqueous RAFT polymerization. Macromolecules 39(20), 6871-6881 (2006).
50. Greenwald RB, Choe YH, McGuire J, Conover CD: Effective drug delivery by PEGylated drug conjugates. Adv. Drug Deliv. Rev. 55(2), 217-250 (2003).
51. Veronese FM, Pasut G: PEGylation, successful approach to drug delivery. Drug Discov. Today 10(21), 1451-1458 (2005).
52. Roberts MJ, Bentley MD, Harris JM: Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev. 54(4), 459-476 (2002).
53. Otsuka H, Nagasaki Y, Kataoka K: PEGylated nanoparticles for biological and pharmaceutical applications. Adv. Drug. Deliv. Rev. 55(3), 403-419 (2003).
54. Kataoka K, Harada A, Nagasaki Y: Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv. Drug. Deliv. Rev. 47(1), 113-131 (2001).
55. Kakizawa Y, Kataoka K: Block copolymer micelles for delivery of gene and related compounds. Adv. Drug. Deliv. Rev. 54(2), 203-222 (2002).
56. 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. 46(12), 6387-6392 (1986).
57. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K: Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Release 65(1-2), 271-284 (2000).
58. Mao S, Neu M, Germershaus O et al.: Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly (ethylene imine)-graft-poly (ethylene glycol) block copolymer/siRNA polyplexes. Bioconjugate Chem. 17(5), 1209-1218 (2006).
59. 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. Pharm. 236(1), 97-108 (2009).
60. Torchilin VP: Multifunctional nanocarriers. Adv. Drug Deliv. Rev. 58(14), 1532-1555 (2006).
61. Forssen E, Willis M: Ligand-targeted liposomes. Adv. Drug Deliv. Rev. 29(3), 249-271 (1998).
62. Davis ME, Chen Z, Shin DM: Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7(9), 771-782 (2008).
63. Schiffelers RM, Ansari A, Xu J et al.: Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res. 32(19), E149 (2004).
64. Kim SH, Mok H, Jeong JH, Kim SW, Park TG: Comparative evaluation of target-specific GFP gene silencing efficiencie for antisense ODN, synthetic siRNA, and siRNA plasmid complexed with PEI-PEG-FOL conjugate. Bioconjugate Chem. 17(1), 241-244 (2007).
65. Forrest ML, Meister GE, Koerber JT, Pack DW: Partial acetylation of polyethylenimine enhances in vitro gene delivery. Pharm. Res. 21(2), 365-371 (2004)
66. Thomas M, Klibanov AM: Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells. Proc. Natl Acad. Sci. USA 99(23), 14640-14645 (2002).
67. Zintchenko A, Philipp A, Dehshahri A, Wagner E: Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. Bioconjugate Chem. 19(7), 1448-1455 (2008).
68. Han SO, Mahato RI, Kim SW: Water-soluble lipopolymer for gene delivery. Bioconjugate Chem. 12(3), 337-345 (2001).
69. Lee M, Rentz J, Han SO, Bull DA, Kim SW: Water-soluble lipopolymer as an efficient carrier for gene delivery to myocardium. Gene Ther. 10(7), 585-593 (2003). (Pubitemid 36432610)
70. Kim WJ, Chang CW, Lee M, Kim SW: Efficient siRNA delivery using water soluble lipopolymer for anti-angiogenic gene therapy. J. Controlled Release 118(3), 357-363 (2007).
71. Philipp A, Zhao X, Tarcha P, Wagner E, Zintchenko A: Hydrophobically modified oligoethylenimines as highly efficient transfection agents for siRNA delivery. Bioconjugate Chem. 20(11), 2055-2061 (2009).
72. Chen J, Tian H, Guo Z et al.: A highly efficient siRNA carrier of PBLG modified hyperbranched PEI. Macromol. Biosci. 9 (12) 1247-1253 (2009).
73. Segura T, Hubbell JA: Synthesis and in vitro characterization of an ABC triblock copolymer for siRNA delivery. Bioconjugate Chem. 18(3), 736-745 (2007).
74. De Rouchey J, Schmidt C, Walker GF et al.: Monomolecular assembly of siRNA and poly (ethylene glycol)-peptide copolymers. Biomacromolecules 9(2), 724-732 (2008).
75. Xiong XB, Uludaq H, Lavasanifar A: Biodegradable amphiphilic poly (ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery. Biomaterials 30(2), 242-253 (2009).
76. Toita A, Soma Y, Morimoto N, Akiyoshi K. Cycloamylose-based biomaterial: nanogel of cholesterol-bearing cationic cycloamylose for siRNA delivery. Chem. Lett. 38(11), 1114-1115 (2009).
77. Kim WJ, Christensen LV, Jo S et al.: Cholesteryl oligoarginine delivering vascular endothelial growth factor siRNA effectively inhibits tumor growth in colon adenocarcinoma. Mol. Ther. 14(3), 343-350 (2006).
78. Itaka K, Kanayama N, Nishiyama N et al.: Supramolecular nanocarrier of siRNA from PEG-based block catiomer carrying diamine side chain with distinctive pKa directed to enhance intracellular gene silencing. J. Am. Chem. Soc. 126(42), 13612-13613 (2004).
79. Bartlett DW, Davis ME: Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res. 34(1), 322-333 (2006).
80. Davis ME: The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: From concept to clinic. Mol. Pharm. 6(3), 659-668 (2009).
81. Bartlett DW, Davis ME: Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjugate Chem. 18(2), 456-468 (2007).
82. 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. 99(4), 975-985 (2008).
83. Breunig M, Lungwitz U, Liebl R, Goepferich A: Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. Proc. Natl Acad. Sci. USA 104(36), 14454-14459 (2007).
84. Breunig M, Hozsa C, Lungwitz U et al.: Mechanistic investigation of poly (ethylene imine)-based siRNA delivery: disulfide bonds boost intracellular release of the cargo. J. Controlled Release 130(1), 57-63 (2008).
85. Meister A, Anderson ME: Glutathione. Annu. Rev. Biochem. 52, 711-760 (1983).
86. Kim SH, Jeong JH, Kim T, Kim SW, Bull DA: VEGF siRNA delivery system using arginine-grafted bioreducible poly (disulfide amine). Mol. Pharm. 6(3), 718-726 (2009).
87. Tarcha PJ, Pelisek J, Merdan T et al.: Synthesis and characterization of chemically condensed oligoethylenimine containing β-aminopropionamide linkages for siRNA delivery. Biomaterials 28(25), 3731-3740 (2007).
88. Tietze N, Pelisek J, Philipp A et al.: Induction of apoptosis in murine neuroblastoma by systemic delivery of transferrin-shielded siRNA polyplexes for downregulation of Ran. Oligonucleotides 18(2), 161-174 (2008).
89. Jere D, Xu CX, Arote R, Yun CH, Cho MH, Cho CS: Poly (amino ester) as a carrier for si/shRNA delivery in lung cancer cells. Biomaterials 29(16), 2535-2547 (2008).
90. Shim MS, Kwon YJ: Acid-responsive linear polyethylenimine for efficient, specific, and biocompatible siRNA delivery. Bioconjugate Chem. 20(3), 488-499 (2009).
91. Matsumoto S, Christie RJ, Nishiyama N et al.: Environment-responsive block copolymer micelles with a disulfide cross-linked core for enhanced siRNA delivery. Biomacromolecules 10(1), 119-127 (2009).
92. Oishi M, Nagasaki Y, Itaka K, Nishiyama N, Kataoka K: Lactosylated poly (ethylene glycol)-siRNA conjugate through acid-labile β-thiopropionate linkage to construct pH-sensitive poly-ion complex micelles achieving enhanced gene silencing in hepatoma cells. J. Am. Chem. Soc. 127(6), 1624-1625 (2005).
93. Oishi M, Nagasaki Y, Nishiyama N et al.: Enhanced growth inhibition of hepatic multicellular tumor spheroids by lactosylated poly (ethylene glycol)-siRNA conjugate formulated in PEGylated polyplexes. Chem Bio Chem 2(9), 1290-1297 (2007).
94. Oishi M, Sasaki S, Nagasaki Y, Kataoka K: pH-responsive oligodeoxynucleotide (ODN)-poly (ethylene glycol) conjugate through acid-labile thiopropionate linkage: Preparation and poly-ion complex micelle formation. Biomacromolecules 4(5), 1426-1432 (2003).
95. Wu CH, Wu GY: Receptor-mediated delivery of foreign genes to hepatocytes. Adv. Drug Deliv. Rev. 29(3), 243-248 (1998).
96. Oishi M, Nagatsugi F, Sasaki S, Nagasaki Y, Kataoka K: Smart poly-ion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages. Chem Bio Chem 6(4), 718-725 (2005).
97. Kim SH, Jeong JH, Lee SH, Kim SW, Park TG: PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J. Controlled Release 116(2), 123-129 (2006).
98. Lee SH, Kim SH, Park TG: Intracellular siRNA delivery system using polyelectrolyte complex micelles prepared from VEGF siRNA-PEG conjugate and cationic fusogenic peptide. Biochem. Biophys. Res. Commun. 357(2), 511-516 (2007).
99. 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. Controlled Release 129(2), 107-116 (2008).
100. Meyer M, Philipp A, Oskuee R, Schmidt C, Wagner E: Breathing life into polycations: Functionalization with pH-responsive endosomolytic peptides and polyethylene glycol enables siRNA delivery. J. Am. Chem. Soc. 130(11), 3272-3273 (2008).
101. Meyer M, Dohmen C, Philipp A et al.: Synthesis and biological evaluation of a bioresponsive and endosomolytic siRNA-polymer conjugate. Mol. Pharm. 6(3), 752-762 (2009).
102. Lee H, Mok H, Lee S, Oh YK, Park TG: Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels. J. Controlled Release 119(2), 245-252 (2007).
103. York AW, Huang F, McCormick CL: Rational design of targeted cancer therapeutics through the multiconjugation of folate and cleavable siRNA to RAFT-synthesized (HPMA-s-APMA) copolymers. Biomacromolecules 11(2), 505-514 (2010).
104. Heredia KL, Nguyen TH, Chang CW, Bulmus V, Davis TP, Maynard HD: Reversible siRNA-polymer conjugates by RAFT polymerization. Chem. Commun. 3245-3247 (2008).
105. Xu J, Boyer C, Bulmus V, Davis TP: Synthesis of dendritic carbohydrate end-functional polymers via RAFT: Versatile multifunctional precursors for bioconjugations. J. Polym. Sci. A Polym. Chem. 47(17), 4302-4313 (2009).
106. Barlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME: Impact of tumorspecific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl Acad. Sci. USA 104(39), 15549-15554 (2007).
107. Merkel OM, Librizzi D, Pfestroff A et al.: Stability of siRNA polyplexes from poly (ethylenimine) and poly (ethylenimine) - g-poly (ethylene glycol) under in vivo conditions: Effects on pharmacokinetics and biodistribution measured by fluorescence fluctuation spectroscopy and single photon emission computed tomography (SPECT) imaging. J. Controlled Release 138(2), 148-159 (2009).
108. Oishi M, Nagasaki Y: Stimuli-responsive smart nanogels for cancer diagnostics and therapy. Nanomedicine (Lond.) 5(3), 451-468 (2010).
109. Tamura A, Oishi M, Nagasaki Y: Enhanced cytoplasmic delivery of sirna using a stabilized poly-ion complexes based on PEGylated nanogels with a cross-linked polyamine structure. Biomacromolecules 10(7), 1818-1827 (2009).
110. Hu Y, Atukorale PU, Lu JJ et al.: Cytosolic delivery mediated via electrostatic surface binding of protein, virus, or siRNA cargos to pH-responsive core-shell gel particles. Biomacromolecules 10(4), 756-765 (2009).
111. Raemdonck K, Naeye B, Buyens K et al.: Biodegradable dextran nanogels for RNA interference: Focusing on endosomal escape and intracellular siRNA delivery. Adv. Func. Mater. 19(9), 1406-1415 (2009).
112. Blackburn WH, Dickerson EB, Smith MH, McDonald JF, Lyon LA: Peptidefunctionalized nanogels for targeted siRNA delivery. Bioconjugate Chem. 20(5), 960-968 (2009).