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Nanocarrier Mediated Cytosolic Delivery of Drug, DNA and Proteins

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Proceedings of the National Academy of Sciences, India Section B: Biological Sciences Aims and scope Submit manuscript

Abstract

Recent researches have focused on the development of a number of macromolecular drugs such as DNA, protein and drugs that are intended to exert their action in cytosol or other intracellular organelle. The major hurdle encountered in their in vivo utilization is endosomal escape of drugs. The advent in research on nanotechnology has offered a number of optional nanocarriers which demonstrate numerous advantages in specialized drug delivery applications. These advantages include stabilization, controlled release and site specific delivery of therapeutic molecules. In addition, the cytosolic delivery to subcellular compartments can also be achieved by inclusion of pH sensitive molecules (lipid, polymer or peptide) in nanocarrier construct to achieve endosomal escape. A number of molecules have been identified that in combination with nanocarriers mediate cytosolic delivery of bioactives.

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References

  1. Tjelle E, Brech A, Juvet LK, Griffiths G, Berg T (1996) Isolation and characterization of early endosomes, late endosomes and terminal lysosomes: their role in protein degradation. J Cell Sci 109:2905–2914

    PubMed  CAS  Google Scholar 

  2. Juliano RL, Alahari S, Yoo H, Kole R, Cho MJ (1999) Antisense pharmacodynamics: critical issues in the transport and delivery of antisense oligonucleotides. Pharm Res 16:494–502

    PubMed  CAS  Google Scholar 

  3. Braasch DA, Corey DR (2002) Novel antisense and peptide nucleic acid strategies for controlling gene expression. Biochemistry 41:4503–4510

    PubMed  CAS  Google Scholar 

  4. Jeong J, Kim S, Park T (2007) Molecular design of functional polymers for gene therapy. Prog Polym Sci 32:1239–1274

    CAS  Google Scholar 

  5. Miller DK, Griffiths E, Lenard J, Firestone RA (1983) Cell killing by lysosomotropic detergents. J Cell Biol 97:1841–1851

    PubMed  CAS  Google Scholar 

  6. Pack DW, Putnam D, Langer R (2000) Design of imidazole-containing endosomolytic biopolymers for gene delivery. Biotechnol Bioeng 67:217–223

    PubMed  CAS  Google Scholar 

  7. Moreira C, Oliveira H, Pires LR, Simões S, Barbosa MA, Pêgo AP (2009) Improving chitosan-mediated gene transfer by the introduction of intracellular buffering moieties into the chitosan backbone. Acta Biomater 5:2995–3006

    PubMed  CAS  Google Scholar 

  8. Lin C, Engbersen JF (2008) Effect of chemical functionalities in poly (amido amine)s for non-viral gene transfection. J Control Release 132:267–272

    PubMed  CAS  Google Scholar 

  9. Marsh M, Helenius A (1989) Virus entry into animal cells. Adv Virus Res 36:107–151

    PubMed  CAS  Google Scholar 

  10. Horth M, Lambrecht B, Khim MCL, Bex F, Thiriart C, Ruysschaert JM, Burny A, Brasseur R (1991) Theoretical and functional analysis of the SIV fusion peptide. EMBO J 10:2747–2755

    PubMed  CAS  Google Scholar 

  11. Wiley DC, Skehel JJ (1987) The structure and function of the hemagglutinin membrane glycoprotein of Influenza virus. Annu Rev Biochem 56:365–394

    PubMed  CAS  Google Scholar 

  12. Lear JD, Degrado WF (1987) Membrane binding and conformational properties of peptides representing the NH2 terminus of influenza HA-2. J Biol Chem 262:6500–6505

    PubMed  CAS  Google Scholar 

  13. Plank C, Oberhauser B, Mechtler K, Koch C, Wagner E (1994) The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. J Biol Chem 269:12918–12924

    PubMed  CAS  Google Scholar 

  14. Subramanian A, Ma HC, Dahl KN, Zhu JY, Diamond SL (2002) Adenovirus or HA-2 fusogenic peptide-assisted lipofection increases cytoplasmic levels of plasmid in nondividing endothelium with little enhancement of transgene expression. J Gene Med 4:75–83

    PubMed  Google Scholar 

  15. Israelachvili J, Mitchell DJ, Ninham BW (1977) Theory of self assembly of lipid bilayers and vesicles. Biochem Biophys Acta 470:185–201

    PubMed  CAS  Google Scholar 

  16. Cullis PR, Hope MJ, Tilcock CP (1986) Lipid polymorphism and the roles of lipid membranes. Chem Phys Lipids 40:127–144

    PubMed  CAS  Google Scholar 

  17. Szoka FCJ, Yuhong X, Zelphati O (1996) How are nucleic acids released in cells from cationic lipid-nucleic acid complexes? J Liposome Res 6:567–587

    CAS  Google Scholar 

  18. Perrie Y, Frederik PM, Gregoriadis G (2001) Liposome-mediated DNA vaccination: the effect of vesicle composition. Vaccine 19:3301–3310

    PubMed  CAS  Google Scholar 

  19. Khatri K, Goyal AK, Gupta PN, Mishra N, Mehta A, Vyas SP (2008) Surface modified liposomes for nasal delivery of DNA vaccine. Vaccine 26:2225–2233

    PubMed  CAS  Google Scholar 

  20. Huang HW (2004) Molecular mechanism of peptide-induced pores in membranes. Phys Rev Lett 92:198304

    PubMed  Google Scholar 

  21. Yang L, Harroun TA, Weiss TM, Ding L, Huang HW (2001) Barrel-stave model or toroidal model? A case study on melittin pores. Biophys J 81:1475–1485

    PubMed  Google Scholar 

  22. Jenssen H, Hamill P, Hancock R (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511

    PubMed  CAS  Google Scholar 

  23. Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728

    PubMed  CAS  Google Scholar 

  24. Lasic DD (1994) Liposomes: from physics to applications. Biphys J 67:1358–1362

    Google Scholar 

  25. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4:145–160

    PubMed  CAS  Google Scholar 

  26. Allen TM, Hansen CB, Lopes de Menezes DE (1995) Pharmacokinetics of long-circulating liposomes. Adv Drug Deliv Rev 16:267–284

    CAS  Google Scholar 

  27. Litzinger DC, Huang L (1992) Phosphatidylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications. Biochim Biophys Acta 1113:201–227

    PubMed  CAS  Google Scholar 

  28. Drummond DC, Zignani M, Leroux JC (2000) Current status of pH-sensitive liposomes in drug delivery. Prog Lipid Res 39:409–460

    PubMed  CAS  Google Scholar 

  29. Epand RM, Cheetham JJ, Raymer KE (1988) Acid-induced fusion of liposomes: studies with 2,3-seco-5a-cholestan-2,3-dioic acid. Biochim Biophys Acta 940:85–92

    PubMed  CAS  Google Scholar 

  30. Brown PM, Silvius JR (1989) Stability and fusion of lipid vesicles containing head group-modified analogues of phosphatidylethanolamine. Biochim Biophys Acta 980:181–190

    PubMed  CAS  Google Scholar 

  31. Collins D, Litzinger DC, Huang L (1990) Structural and functional comparisons of pH-sensitive liposomes composed of phosphatidylethanolamine and three different diacylsuccinylglycerols. Biochim Biophys Acta 1025:234–242

    PubMed  CAS  Google Scholar 

  32. Cullis PR, de Kruijff B (1979) Lipid polymorphism and the functional roles of lipids in biological membranes. Biochim Biophys Acta 559:399–420

    PubMed  CAS  Google Scholar 

  33. Connor J, Huang L (1985) Efficient cytoplasmic delivery of a fluorescent dye by pH-sensitive immunoliposomes. J Cell Biol 101:582–589

    PubMed  CAS  Google Scholar 

  34. Straubinger RM, Duzgunes N, Papahadjopoulos D (1985) pH-sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules. FEBS Lett 179:148–154

    PubMed  CAS  Google Scholar 

  35. Simoes S, Slepushkin V, Duzgunes N, Pedroso de Lima MC (2001) On the mechanisms of internalization and intracellular delivery mediated by pH-sensitive liposomes. Biochim Biophys Acta 1515:23–37

    PubMed  CAS  Google Scholar 

  36. Duzgunes N, Straubinger RM, Baldwin PA, Friend DS, Papahadjopoulos D (1985) Proton-induced fusion of oleic acid/phosphatidylethanolamine liposomes. Biochemistry 24:3091–3098

    PubMed  CAS  Google Scholar 

  37. Bergstranda N, Arfvidssona MC, Kimb JM, Thompson DH, Edwardsa K (2003) Interactions between pH-sensitive liposomes and model membranes. Biophys Chem 104:361–379

    Google Scholar 

  38. Huth US, Schubert R, Peschka-Suss R (2006) Investigating the uptake and intracellular fate of pH-sensitive liposomes by flow cytometry and spectral bio-imaging. J Control Release 110:490–504

    PubMed  CAS  Google Scholar 

  39. Morilla MJ, Montanari J, Frank F, Malchiodi E, Corral R, Petray P, Romero EL (2005) Etanidazole in pH-sensitive liposomes: design, characterization and in vitro/in vivo anti-Trypanosoma cruzi activity. J Control Release 103:599–607

    PubMed  CAS  Google Scholar 

  40. Costin GE, Trif M, Nichita N, Dwek RA, Petrescua SM (2002) pH-sensitive liposomes are efficient carriers for endoplasmic reticulum-targeted drugs in mouse melanoma cells. Biochem Biophy Res Commun 293:918–923

    CAS  Google Scholar 

  41. Shi G, Guo W, Stephenson SM, Lee RJ (2002) Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations. J Control Release 80:309–319

    PubMed  CAS  Google Scholar 

  42. Obata Y, Tajima S, Takeoka S (2010) Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo. J Control Release 142:267–276

    PubMed  CAS  Google Scholar 

  43. Oliveira MCD, Fattal E, Ropert C, Malvy C, Couvreura P (1997) Delivery of antisense oligonucleotides by means of pH-sensitive liposomes. J Control Release 48:179–184

    Google Scholar 

  44. Chang JS, Choi MJ, Cheong HS, Kim K (2001) Development of Th1-mediated CD8+ effector T cells by vaccination with epitope peptides encapsulated in pH-sensitive liposomes. Vaccine 19:3608–3614

    PubMed  CAS  Google Scholar 

  45. Vyas SP, Jadon RS, Goyal AK, Mishra N, Gupta PN, Khatri K, Tyagi R (2008) pH sensitive liposomes enhances immunogenicity of 19 kDa carboxyl-terminal fragment of Plasmodium falciparum. Int J Pharm Sci Nanotechnol 1:78–86

    CAS  Google Scholar 

  46. Nair S, Zhou F, Reddy K, Huang SL, Rouse BT (1992) Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro. J Exp Med 9:609–661

    Google Scholar 

  47. Chikh G, Schutze-Redelmeir MP (2002) Liposomal delivery of CTL epitopes to dendritic cells. Biosci Rep 22:339–353

    PubMed  CAS  Google Scholar 

  48. Kono K, Zenitani K, Takagishi T (1994) Novel pH-sensitive liposomes: liposomes bearing a poly(ethylene glycol) derivative with carboxyl groups. Biochim Biophys Acta 1193:1–9

    PubMed  CAS  Google Scholar 

  49. Puyal C, Maurin L, Miquel G, Bienvenue A, Philip-Pot J (1994) Design of a short membrane-destabilizing peptide covalently bound to liposomes. Biochim Biophys Acta 1195:259–266

    PubMed  Google Scholar 

  50. Murata M, Sugahara Y, Takahashi S, Ohnishi SI (1987) pH-dependent membrane fusion activity of a synthetic twenty amino acid peptide with the same sequence as that of the hydrophobic segment of influenza virus haemagglutinin. J Biochem 102:957–962

    PubMed  CAS  Google Scholar 

  51. Murata M, Takahashi S, Kagiwada S, Suzuki A, Ohnishi S (1992) pH-dependent membrane fusion activity of a synthetic twenty amino acid peptide with the same sequence as that of the hydrophobic segment of influenza virus haemagglutinin. Biochemistry 31:1986–1992

    PubMed  CAS  Google Scholar 

  52. Kono K, Nishii H, Takagishi T (1993) Fusion activity of an amphiphilic polypeptide having acidic amino acid residues: generation of fusion activity by alpha-helix formation and charge neutralization. Biochim Biophys Acta 1164:81–90

    PubMed  CAS  Google Scholar 

  53. Schwarze SR, Hruska KA, Dowdy SF (2000) Protein transduction: unrestricted delivery into all cells? Trends Cell Biol 10:290–295

    PubMed  CAS  Google Scholar 

  54. Lindgren M, Hallbrink M, Prochiantz A, Langel U (2000) Cell-penetrating peptides. Trends Pharmacol Sci 21:99–103

    PubMed  CAS  Google Scholar 

  55. Dietz GP, Bahr M (2004) Delivery of bioactive molecules into the cell: the Trojan horse approach. Mol Cell Neurosci 27:85–131

    PubMed  CAS  Google Scholar 

  56. Snyder EL, Dowdy SF (2004) Cell penetrating peptides in drug delivery. Pharm Res 21:389–393

    PubMed  CAS  Google Scholar 

  57. Trehin R, Merkle HP (2004) Chances and pitfalls of cell penetrating peptides for cellular drug delivery. Eur J Pharm Biopharm 58:209–223

    PubMed  CAS  Google Scholar 

  58. Gupta B, Levchenko TS, Torchilin VP (2005) Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev 57:637–651

    PubMed  CAS  Google Scholar 

  59. Torchilin VP, Levchenko TS, Rammohan R, Volodina N, Papahadjopoulos-Sternberg B, D’Souza GG (2003) Cell transfection in vitro and in vivo with nontoxic TAT peptide–liposome–DNA complexes. Proc Natl Acad Sci USA 100:1972–1977

    PubMed  CAS  Google Scholar 

  60. Jarver P, Langel U (2004) The use of cell-penetrating peptides as a tool for gene regulation. Drug Discov Today 9:395–402

    PubMed  Google Scholar 

  61. Wagner E, Plank C, Zatloukal K, Cotten M, Birnstiel ML (1992) Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin–polylysine–DNA complexes: toward a synthetic virus-like gene transfer vehicle. Proc Natl Acad Sci USA 89:7934–7938

    PubMed  CAS  Google Scholar 

  62. Oliveira S, van Rooy I, Kranenburg O, Storm G, Schiffelers RM (2007) Fusogenic peptides enhance endosomal escape improving siRNA-induced silencing of oncogenes. Int J Pharm 331:211–214

    PubMed  CAS  Google Scholar 

  63. Funhoff AM, Van Nostrum CF, Janssen APCA, Fens MHAM, Crommelin DJA, Hennink WE (2004) Polymer side-chain degradation as a tool to control the destabilization of polyplexes. Pharm Res 21:170–176

    PubMed  CAS  Google Scholar 

  64. Funhoff AM, Van Nostrum CF, Lok MC, Fretz MM, Crommelin DJA, Hennink WE (2004) Poly(3-guanidinopropyl methacrylate): a novel cationic polymer for gene delivery. Bioconjug Chem 15:1212–1220

    PubMed  CAS  Google Scholar 

  65. Jiang X, Lok MC, Hennink WE (2007) Degradable-brushed pHEMA-pDMAEMA synthesized via ATRP and click chemistry for gene delivery. Bioconjug Chem 18:2077–2084

    PubMed  CAS  Google Scholar 

  66. Simeoni F, Morris MC, Heitz F, Divita G (2003) Insight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells. Nucleic Acids Res 31:2717–2724

    PubMed  CAS  Google Scholar 

  67. Beerens AM, Al Hadithy AF, Rots MG, Haisma HJ (2003) Protein transduction domains and their utility in gene therapy. Curr Gene Ther 3:486–494

    PubMed  CAS  Google Scholar 

  68. Lo SL, Wang S (2008) An endosomolytic Tat peptide produced by incorporation of histidine and cysteine residues as a nonviral vector for DNA transfection. Biomaterials 29:2408–2414

    PubMed  CAS  Google Scholar 

  69. Kimura T, Ohyama A (1988) Association between the pH-dependent conformational change of West Nile flavivirus E protein and virus-mediated membrane fusion. J Gen Virol 69:1247–1254

    PubMed  CAS  Google Scholar 

  70. Tweten RK (2005) Cholesterol-dependent cytolysins, a family of versatile poreforming toxins. Infect Immun 73:6199–6209

    PubMed  CAS  Google Scholar 

  71. Lorenzi GL, Lee KD (2005) Enhanced plasmid DNA delivery using anionic LPDII by listeriolysin O incorporation. J Gene Med 7:1077–1085

    PubMed  CAS  Google Scholar 

  72. Kullberg M, Owens JL, Mann K (2010) Listeriolysin O enhances cytoplasmic delivery by Her-2 targeting liposomes. J Drug Target 18:313–320

    PubMed  CAS  Google Scholar 

  73. Saito G, Amidon GL, Lee KD (2003) Enhanced cytosolic delivery of plasmid DNA by a sulfhydryl-activatable listeriolysin O/protamine conjugate utilizing cellular reducing potential. Gene Ther 10:72–83

    PubMed  CAS  Google Scholar 

  74. Browne KA, Blink E, Sutton VR, Froelich CJ, Jans DA, Trapani JA (1999) Cytosolic delivery of granzyme B by bacterial toxins: evidence that endosomal disruption, in addition to transmembrane pore formation, is an important function of perforin. Mol Cell Biol 19:8604–8615

    PubMed  CAS  Google Scholar 

  75. Kakimoto S, Hamada T, Komatsu Y, Takagi M, Tanabe T, Azuma H, Shinkai S, Nagasaki T (2009) The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection. Biomaterials 30:402–408

    PubMed  CAS  Google Scholar 

  76. Barati S, Chegini F, Hurtado P, Rush RA (2002) Hybrid tetanus toxin C fragment diphtheria toxin translocation domain allows specific gene transfer into PC12 cells. Exp Neurol 177:75–87

    PubMed  CAS  Google Scholar 

  77. Teter K, Holmes RK (2002) Inhibition of endoplasmic reticulum-associated degradation in CHO cells resistant to cholera toxin, Pseudomonas aeruginosa exotoxin A, and ricin. Infect Immun 70:6172–6179

    PubMed  CAS  Google Scholar 

  78. Jia LT, Zhang LH, Yu CJ, Zhao J, Xu YM, Gui JH, Jin M, Ji ZL, Wen WH, Wang CJ, Chen SY, Yang AG (2003) Specific tumoricidal activity of a secreted proapoptotic protein consisting of HER2 antibody and constitutively active caspase-3. Cancer Res 63:3257–3262

    PubMed  CAS  Google Scholar 

  79. Bruell D, Stöcker M, Huhn M, Redding N, Küpper M, Schumacher P, Paetz A, Bruns CJ, Haisma HJ, Fischer R, Finnern R, Barth S (2003) The recombinant anti-EGF receptor immunotoxin 425(scFv)-ETA′ suppresses growth of a highly metastatic pancreatic carcinoma cell line. Int J Oncol 23:1179–1186

    PubMed  CAS  Google Scholar 

  80. Sun J, Pohl EE, Krylova OO, Krause E, Agapov II, Tonevitsky AG, Pohl P (2004) Membrane destabilization by ricin. Eur Biophys J 33:572–579

    PubMed  CAS  Google Scholar 

  81. Tu Y, Kim JS (2008) A fusogenic segment of glycoprotein H from herpes simplex virus enhances transfection efficiency of cationic liposomes. J Gene Med 10:646–654

    PubMed  CAS  Google Scholar 

  82. Lee H, Jeong JH, Park TG (2001) A new gene delivery formulation of polyethylenimine/DNA complexes coated with PEG conjugated fusogenic peptide. J Control Release 76:183–192

    PubMed  CAS  Google Scholar 

  83. Han J, Yeom YI (2000) Specific gene transfer mediated by galactosylated poly-l-lysine into hepatoma cells. Int J Pharm 202:151–160

    PubMed  CAS  Google Scholar 

  84. Min SH, Lee DC, Lim MJ, Park HS, Kim DM, Cho CW, Yoon DY, Yeom YI (2006) A composite gene delivery system consisting of polyethylenimine and a amphipathic peptide KALA. J Gene Med 8:1425–1434

    PubMed  CAS  Google Scholar 

  85. Futaki S, Masui Y, Nakase I, Sugiura Y, Nakamura T, Kogure K, Harashima H (2005) Unique features of a pH-sensitive fusogenic peptide that improves the transfection efficiency of cationic liposomes. J Gene Med 7:1450–1458

    PubMed  CAS  Google Scholar 

  86. Sasaki K, Kogure K, Chaki S, Nakamura Y, Moriguchi R, Hamada H, Danev R, Nagayama K, Futaki S, Harashima H (2008) An artificial virus-like nano carrier system: enhanced endosomal escape of nanoparticles via synergistic action of pH-sensitive fusogenic peptide derivatives. Anal Bioanal Chem 391:2717–2727

    PubMed  CAS  Google Scholar 

  87. Kakudo T, Chaki S, Futaki S, Nakase I, Akaji K, Kawakami T, Maruyama K, Kamiya H, Harashima H (2004) Transferrin-modified liposomes equipped with a pH sensitive fusogenic peptide: an artificial viral-like delivery system. Biochemistry 43:5618–5628

    PubMed  CAS  Google Scholar 

  88. White JM (1990) Viral and cellular membrane fusion proteins. Annu Rev Physiol 52:675–697

    PubMed  CAS  Google Scholar 

  89. Skehel JJ, Bayley PM, Brown EB, Martin SR, Waterfield MD, White JM, Wilson IA, Wiley DC (1982) Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci USA 79:968–972

    PubMed  CAS  Google Scholar 

  90. Doms RW, Helenius A, White J (1985) Membrane fusion activity of the influenza virus haemagglutinin: the low pH-induced conformational change. J Biol Chem 260:2973–2981

    PubMed  CAS  Google Scholar 

  91. Harter C, James P, Bachi T, Semenza G, Brunner J (1989) Hydrophobic binding of the ectodomain of influenza hemagglutinin to membranes occurs through the “fusion peptide”. J Biol Chem 264:6459–6464

    PubMed  CAS  Google Scholar 

  92. Stegmann T, Delfino JM, Richards FM, Helenius A (1991) The HA2 subunit of influenza hemagglutinin inserts into the target membrane prior to fusion. J Biol Chem 266:18404–18410

    PubMed  CAS  Google Scholar 

  93. Wagner E (1999) Application of membrane-active peptides for nonviral gene delivery. Adv Drug Deliv Rev 38:279–289

    PubMed  CAS  Google Scholar 

  94. Zuidam NJ, Posthuma G, de Vries ET, Crommelin DJ, Hennink WE, Storm G (2000) Effects of physicochemical characteristics of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes on cellular association and internalisation. J Drug Target 8:51–66

    PubMed  CAS  Google Scholar 

  95. Van Rossenberg SM, Sliedregt-Bol KM, Meeuwenoord NJ, Van Berkel TJ, Van Boom JH, Van Der Marel GA, Biessen EA (2002) Targeted lysosome disruptive elements for improvement of parenchymal liver cell-specific gene delivery. J Biol Chem 277:45803–45810

    PubMed  Google Scholar 

  96. Khalil IA, Kogure K, Futaki S, Harashima H (2008) Octaarginine-modified liposomes: enhanced cellular uptake and controlled intracellular trafficking. Int J Pharm 354:39–48

    PubMed  CAS  Google Scholar 

  97. Homhuan A, Kogure K, Nakamura T, Shastri N, Harashima H (2009) Enhanced antigen presentation and CTL activity by transduction of mature rather than immature dendritic cells with octaarginine-modified liposomes. J Control Release 136:79–85

    PubMed  CAS  Google Scholar 

  98. Bungener L, Serre K, Bijl L, Leserman L, Wilschut J, Daemena T, Machy P (2002) Virosome-mediated delivery of protein antigens to dendritic cells. Vaccine 20:2287–2295

    PubMed  CAS  Google Scholar 

  99. Schoen P, Chonn A, Cullis PR, Wilschut J, Scherrer P (1999) Gene transfer mediated by fusion protein haemagglutinin reconstituted in cationic lipid vesicles. Gene Ther 6:823–832

    PubMed  CAS  Google Scholar 

  100. Prochiantz A (2000) Messenger proteins: homeo proteins, TAT and others. Curr Opin Cell Biol 12:400–406

    PubMed  CAS  Google Scholar 

  101. Torchilin VP, Rammohan R, Weissig V, Levchenko TS (2001) TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc Natl Acad Sci USA 98:8786–8791

    PubMed  CAS  Google Scholar 

  102. Tseng YL, Liu JJ, Hong RL (2002) Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: a kinetic and efficacy study. Mol Pharmacol 62:864–872

    PubMed  CAS  Google Scholar 

  103. Lundberg M, Johansson M (2002) Positively charged DNA-binding proteins cause apparent cell membrane translocation. Biochem Biophys Res Commun 291:367–371

    PubMed  CAS  Google Scholar 

  104. Richard JP, Melikov K, Vives E, Ramos C, Verbeure B, Gait MJ, Chernomordik LV, Lebleu B (2002) Cell-penetrating peptides: a revaluation of the mechanism of cellular uptake. J Biol Chem 278:585–590

    PubMed  Google Scholar 

  105. Fretza MM, Koninga GA, Mastrobattistaa E, Jiskoota W, Storm G (2004) OVCAR-3 cells internalize TAT-peptide modified liposomes by endocytosis. Biochim Biophys Acta 1665:48–56

    Google Scholar 

  106. Li W, Nicol F, Szoka FC (2004) GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv Drug Deliv Rev 56:967–985

    PubMed  CAS  Google Scholar 

  107. Yamada Y, Shinoharab Y, Kakudoa T, Chakia S, Futakic S, Kamiyaa H, Hideyoshi H (2005) Mitochondrial delivery of mastoparan with transferrin liposomes equipped with a pH-sensitive fusogenic peptide for selective cancer therapy. Int J Pharm 303:1–7

    PubMed  CAS  Google Scholar 

  108. Kono K, Igawa T, Takagishi T (1997) Cytoplasmic delivery of calcein mediated by liposomes modified with a pH-sensitive poly-ethylene glycol/derivative. Biochim Biophys Acta 1325:143–154

    PubMed  CAS  Google Scholar 

  109. Kono K, Henmi A, Yamashita H, Hayashi H, Takagishi T (1999) Improvement of temperature-sensitivity of poly(N-isopropylacrylamide)-modified liposomes. J Control Release 59:63–75

    PubMed  CAS  Google Scholar 

  110. Yoshino K, Kadowaki A, Takagishi T, Kono K (2004) Temperature sensitization of liposomes by use of N-isopropylacrylamide copolymers with varying transition endotherms. Bioconjug Chem 15:1102–1109

    PubMed  CAS  Google Scholar 

  111. Zhang K, Wu XY (2004) Temperature and pH-responsive polymeric composite membranes for controlled delivery of proteins and peptides. Biomaterials 25:5281–5291

    PubMed  CAS  Google Scholar 

  112. Leroux JC, Roux E, Le Garrec D, Hong K, Drummond DC (2001) N-isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles. J Control Release 72:71–84

    PubMed  CAS  Google Scholar 

  113. Roux E, Stomp R, Giasson S, Pézolet M, Moreau P, Leroux JC (2002) Stearic stabilization of liposomes by pH-responsive N-isopropylacrylamide copolymer. J Pharm Sci 91:1795–1802

    PubMed  CAS  Google Scholar 

  114. Roux E, Passirani C, Scheffold S, Benoit JP, Leroux JC (2004) Serum-stable and long circulating, PEGylated pH-sensitive liposomes. J Control Release 94:447–451

    PubMed  CAS  Google Scholar 

  115. Bertrand N, Fleischer JG, Wasan KM, Leroux JC (2009) Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the design of pH-sensitive liposomes. Biomaterials 30:2598–2605

    PubMed  CAS  Google Scholar 

  116. Simard P, Leroux JC (2009) pH-sensitive immunoliposomes specific to the CD33 cell surface antigen of leukemic cells. Int J Pharm 381:86–96

    PubMed  CAS  Google Scholar 

  117. Hong YJ, Pyo CG, Kim JC (2010) Liposomes incorporating hydrophobically modified silk fibroin: pH-dependent release. Int J Biol Macromol 47:635–639

    PubMed  CAS  Google Scholar 

  118. Wan W, Yang L, Padavan DT (2007) Use of degradable and nondegradable nanomaterials for controlled release. Nanomedicine 2:483–509

    PubMed  CAS  Google Scholar 

  119. Zhou CZ, Confalonieri F, Jacquet M, Perasso R, Li ZG, Janin J (2001) Silk fibroin: structural implications of a remarkable amino acid sequence. Proteins 44:119–122

    PubMed  CAS  Google Scholar 

  120. Meinel AJ, Kubow KE, Klotzsch E, Garcia-Fuentes M, Smith ML, Vogel V, Merkle HP, Meinel L (2009) Optimization strategies for electrospun silk fibroin tissue engineering scaffolds. Biomaterials 30:3058–3067

    PubMed  CAS  Google Scholar 

  121. Breslauer DN, Muller SJ, Lee LP (2010) Generation of monodisperse silk microspheres prepared with microfluidics. Biomacromolecules 11:643–647

    PubMed  CAS  Google Scholar 

  122. Sakaguchi N, Kojima C, Harada A, Kono K (2008) Preparation of pH-sensitive poly (glycidol) derivatives with varying hydrophobicities: their ability to sensitize stable liposomes to pH. Bioconjug Chem 19:1040–1048

    PubMed  CAS  Google Scholar 

  123. Yuba E, Harada A, Sakanishi Y, Kono K (2011) Carboxylated poly(glycidol)s for preparation of pH-sensitive liposomes. J Control Release 149:72–80

    PubMed  CAS  Google Scholar 

  124. Yuba E, Kojima C, Atsushi H, Shinobu Watarai T, Kono K (2010) pH-sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity. Biomaterials 31:943–951

    PubMed  CAS  Google Scholar 

  125. Vasir JK, Labhasetwar V (2007) Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev 59:718–728

    PubMed  CAS  Google Scholar 

  126. Zelphati O, Wang Y, Kitada S, Reed JC, Felgner PL, Corbeil J (2001) Intracellular delivery of proteins with a new lipid-mediated delivery system. J Biol Chem 276:35103–35110

    PubMed  CAS  Google Scholar 

  127. Vyas SP, Gupta M, Mishra N, Dube D (2010) In: Felton GP (ed) Block copolymers based nanoconstructs: importance in drug delivery. Nova Science Publishers, New York, p 273

  128. Torchilin V (2008) Intracellular delivery of protein and peptide therapeutics. Drug Discov Today 5:e95–e103

    Google Scholar 

  129. Allen T, Cullis P (2004) Drug delivery systems: entering the mainstream. Science 303:1818–1822

    PubMed  CAS  Google Scholar 

  130. Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2:347–360

    PubMed  CAS  Google Scholar 

  131. Uchegb IF, Anderson S, Brownlie A (2006) In: Uchegbu IF, Schatzlein AG (eds) Polymeric vesicles. Taylor & Francis Inc./CRC Press, Boca Raton, p 131

  132. Cartiera MS, Johnson KM, Rajendran V, Caplan MJ, Saltzman WM (2009) The uptake and intracellular fate of PLGA nanoparticles in epithelial cells. Biomaterials 30:2790–2798

    PubMed  CAS  Google Scholar 

  133. Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515

    PubMed  CAS  Google Scholar 

  134. Hillaireau H, Couvreur P (2006) In: Uchegbu IF, Schatzlein AG (eds) Polymeric nanoparticles as drug carriers. Taylor & Francis Inc./CRC Press, LLC, Boca Raton, p 101

  135. Moghimin SM, Vega E, Garcia ML, Al-Hanbali O, Rutt KJ (2006) In: Torchillin VP (ed) Polymeric nanoparticulates as drug carriers and controlled release implant devices. Imperial College Press, London, p 29

  136. Cho HK, Cheong IW, Lee JM, Kim JH (2010) Polymeric nanoparticles, micelles and polymersomes from amphiphilic block copolymer. Korean J Chem Eng 27:731–740

    CAS  Google Scholar 

  137. Brigger I, Dubernet C, Couvreur P (2002) Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 54:631–651

    PubMed  CAS  Google Scholar 

  138. Khan A, Benboubetra M, Sayyed PZ, Ng KW, Fox S, Beck G, Benter IF, Akhtar S (2004) Sustained polymeric delivery of gene silencing antisense ODNs, siRNA, DNAzymes and ribozymes: in vitro and in vivo studies. J Drug Target 12:393–404

    PubMed  CAS  Google Scholar 

  139. Perlstein I, Connolly JM, Cui X, Song C, Li Q, Jones PL, Lu Z, DeFelice S, Klugherz B, Wilensk R, Levy RJ (2003) DNA delivery from an intravascular stent with a denatured collagen-polylactic-polyglycolic acid-controlled release coating: mechanisms of enhanced transfection. Gene Ther 10:1420–1428

    PubMed  CAS  Google Scholar 

  140. Shen Y, Tang H, Zhan Y, Van Kirk EA, Murdoch WJ (2009) Degradable Poly(β-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine 5:192–201

    PubMed  Google Scholar 

  141. Na K, Lee ES, Bae YH (2003) Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH dependent cell interaction, internalization and cytotoxicity in vitro. J Control Release 87:3–13

    PubMed  CAS  Google Scholar 

  142. Xu P, VanKirk EA, Murdoch WJ, Zhan Y, Isaak DD, Radosz M, Shen Y (2006) Anticancer efficacies of cisplatin-releasing pH-responsive nanoparticles. Biomacromolecules 7:829–835

    PubMed  CAS  Google Scholar 

  143. Anderson DG, Akinc A, Hossain N, Langer R (2005) Structure/property studies of polymeric gene delivery using a library of poly(beta-amino esters). Mol Ther 11:426–434

    PubMed  CAS  Google Scholar 

  144. Lynn DM, Amiji MM, Langer R (2001) pH-responsive biodegradable polymer microspheres: rapid release of encapsulated material within the range of intracellular pH. Angew Chem Int Ed 40:1707–1710

    CAS  Google Scholar 

  145. Potineni A, Lynn DM, Langer R, Amiji MM (2003) Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery. J Control Release 86:223–234

    PubMed  CAS  Google Scholar 

  146. Devalapally H, Shenoy D, Little S, Langer R, Amiji M (2007) Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 3. Therapeutic efficacy and safety studies in ovarian cancer xenograft model. Cancer Chemother Pharmacol 59:477–484

    PubMed  CAS  Google Scholar 

  147. Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit JP (2008) Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials 29:3477–3496

    PubMed  CAS  Google Scholar 

  148. Panyam J, Zhou WZ, Prabha S, Sahoo SK, Labhasetwar V (2002) Rapid endolysosomal escape of poly(d,l-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J J16:1217–1226

    Google Scholar 

  149. Zhang XQ, Intra J, Salem AK (2008) Comparative study of poly (lactic-co-glycolicacid)-poly ethyleneimine-plasmid DNA microparticles prepared using double emulsion methods. J Microencapsul 25:1–12

    PubMed  Google Scholar 

  150. Patil Y, Panyam J (2009) Polymeric nanoparticles for siRNA delivery and gene silencing. Int J Pharm 367:195–203

    PubMed  CAS  Google Scholar 

  151. Fattal E, Bochot A (2008) State of the art and perspectives for the delivery of antisense oligonucleotides and siRNA by polymeric nanocarriers. Int J Pharm 364:237–248

    PubMed  CAS  Google Scholar 

  152. Chavany C, Le Doan T, Couvreur P, Puisieux F, Helene C (1992) Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides. Pharm Res 9:441–449

    PubMed  CAS  Google Scholar 

  153. Chavany C, Saison-Behmoaras T, Le Doan T, Puisieux F, Couvreur P, Helene C (1994) Adsorption of oligonucleotides onto polyisohexylcyanoacrylate nanoparticles protects them against nucleases and increases their cellular uptake. Pharm Res 11:1370–1378

    PubMed  CAS  Google Scholar 

  154. Tahara K, Sakai T, Yamamoto H, Takeuchi H, Hirashima N, Kawashima Y (2009) Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells. Int J Pharm 382:198–204

    PubMed  CAS  Google Scholar 

  155. Tahara K, Yamamoto H, Kawashima Y (2010) Cellular uptake mechanisms and intracellular distributions of polysorbate 80-modified poly (d,l-lactide-co-glycolide) nanospheres for gene delivery. Eur J Pharm Biopharm 75:218–224

    PubMed  CAS  Google Scholar 

  156. Jain AK, Goyal AK, Gupta PN, Khatri K, Mishra N, Mehta A, Mangal S, Vyas SP (2009) Synthesis, characterization and evaluation of novel triblock copolymer based nanoparticles for vaccine delivery against hepatitis B. J Control Release 136:161–169

    PubMed  CAS  Google Scholar 

  157. Leite EA, Giuberti CS, Wainstein AJA, Wainstein APDL, Coelho LG, Lana ÂMQ, Savassi-Rocha PR, Oliveira MCD (2009) Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration. Life Sci 84:641–649

    PubMed  CAS  Google Scholar 

  158. Barea MJ, Jenkins MJ, Gaber MH, Bridson RH (2010) Evaluation of liposomes coated with a pH responsive polymer. Int J Pharm 402:89–94

    PubMed  CAS  Google Scholar 

  159. Yang X, Lee HY, You SG, Kim JC (2009) pH- and temperature-dependent release from cationic vesicles coexisting with copolymer of N-isopropylacrylamide and methacrylic acid. Colloid Surfaces A 348:109–115

    CAS  Google Scholar 

  160. Wang C, Ho PC, Lim LY (2010) Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells. Int J Pharm 400:201–210

    PubMed  CAS  Google Scholar 

  161. Kang HC, Samsonova O, Bae YH (2010) Trafficking micro environmental pH of polycationic gene vectors in drug-sensitive and multidrug-resistant MCF7 breast cancer cells. Biomaterials 31:3071–3078

    PubMed  CAS  Google Scholar 

  162. Acharya S, Dilnawaz F, Sahoo SK (2009) Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy. Biomaterials 30:5737–5750

    PubMed  CAS  Google Scholar 

  163. Cho SK, Kwon YJ (2011) Polyamine/DNA polyplexes with acid-degradable polymeric shell as structurally and functionally virus-mimicking nonviral vectors. J Control Release 150:287–297

    PubMed  CAS  Google Scholar 

  164. Liu J, Jiang Z, Zhang S, Saltzman WM (2009) Poly(ω-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery. Biomaterials 30:5707–5719

    PubMed  CAS  Google Scholar 

  165. Gargouri M, Sapin A, Arıca-Yegin B, Merlin JL, Becuwe P, Maincent P (2011) Photochemical internalization for pDNA transfection: evaluation of poly(d, l-lactide-co-glycolide) and poly(ethylenimine) nanoparticles. Int J Pharm 403:276–284

    PubMed  CAS  Google Scholar 

  166. Misra R, Sahoo SK (2010) Intracellular trafficking of nuclear localization signal conjugated nanoparticles for cancer therapy. Eur J Pharm Sci 39:152–163

    PubMed  CAS  Google Scholar 

  167. Tsai HC, Chang WH, Lo CL, Tsai CH, Chang CH, Ou TW, Yen TC, Hsiue GH (2010) Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging. Biomaterials 31:2293–2301

    PubMed  CAS  Google Scholar 

  168. Ditto AJ, Shah P, Lopina ST, Yun YH (2009) Nanospheres formulated from l-tyrosine polyphosphate as a potential intracellular delivery device. Int J Pharm 368:199–206

    PubMed  CAS  Google Scholar 

  169. Fay F, Quinn DJ, Gilmore BF, McCarron PA, Scott CJ (2010) Gene delivery using dimethyldidodecylammonium bromide-coated PLGA nanoparticles. Biomaterials 31:4214–4222

    PubMed  CAS  Google Scholar 

  170. Peng SF, Yang MJ, Su CJ, Chen HL, Lee PW, Wei MC, Sung HW (2009) Effects of incorporation of poly(γ-glutamic acid) in chitosan/DNA complex nanoparticles on cellular uptake and transfection efficiency. Biomaterials 30:1797–1808

    PubMed  CAS  Google Scholar 

  171. Shim MS, Kwon YJ (2009) Controlled cytoplasmic and nuclear localization of plasmid DNA and siRNA by differentially tailored polyethylenimine. J Control Release 133:206–213

    PubMed  CAS  Google Scholar 

  172. Ng CP, Goodman TT, Park IK, Pun SH (2009) Bio-mimetic surface engineering of plasmid-loaded nanoparticles for active intracellular trafficking by actin comet-tail motility. Biomaterials 30:951–958

    PubMed  CAS  Google Scholar 

  173. Gupta M, Vyas SP (2010) In: Vyas SP, Murthy RSR, Narang RK (eds) Role of polymeric nanocarriers for cancer chemotherapy. CBS Publishers, New Delhi, p 365

  174. Rapoport N (2007) Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Prog Polym Sci 32:962–990

    CAS  Google Scholar 

  175. Adams ML, Lavasanifar A, Kwon GS (2003) Amphiphilic block copolymers for drug delivery. J Pharm Sci 92:1343–1355

    PubMed  CAS  Google Scholar 

  176. Torchilin VP (2010) Polymeric micelles for therapeutic applications in medicine. In: Broz P (ed) Polymer based nanostructures: medical applications. RSC nanoscience and nanotechnology. Royal Society of Chemistry, Cambridge, pp 261–299

  177. Cho K, Wang X, Nie S, Georgia Z, Dong C, Shin M (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316

    PubMed  CAS  Google Scholar 

  178. van Vlerken LE, Vyas TK, Amiji MM (2007) Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res 24:1405–1414

    PubMed  Google Scholar 

  179. Wiradharma N, Zhang Y, Venkataraman S, Hedrick JL, Yang YY (2009) Self-assembled polymer nanostructures for delivery of anticancer therapeutics. Nano Today 4:302–317

    CAS  Google Scholar 

  180. Zhang L, Eisenberg A (1995) Multiple morphologies of “crew-cut” aggregates of polystyrene-b-poly(acrylic acid) block copolymers. Science 268:1728–1731

    PubMed  CAS  Google Scholar 

  181. Zhang L, Uyen Nguyen TL, Bernard J, Davis TP, Barner-Kowollik C, Stenzel MH (2007) Shell-cross-linked micelles containing cationic polymers synthesized via the RAFT process: toward a more biocompatible gene delivery system. Biomacromolecules 8:2890–2901

    PubMed  CAS  Google Scholar 

  182. Matsumura Y (2007) Preclinical and clinical studies of anticancer drug-incorporated polymeric micelles. J Drug Target 15:507–517

    PubMed  CAS  Google Scholar 

  183. Gillies ER, Frechet JMJ (2005) pH-responsive copolymer assemblies for controlled release of doxorubicin. Bioconjug Chem 16:361–368

    PubMed  CAS  Google Scholar 

  184. Zhu C, Jung S, Luo S, Meng F, Zhu X, Park TG, Zhong Z (2010) Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA–PCL–PDMAEMA triblock copolymers. Biomaterials 31:2408–2416

    PubMed  CAS  Google Scholar 

  185. Brown MD, Schatzlein AG, Uchegbu IF (2001) Gene delivery with synthetic (non viral) carriers. Int J Pharm 229:1–21

    PubMed  CAS  Google Scholar 

  186. Martimprey H, Vauthier C, Malvy C, Couvreur P (2009) Polymer nanocarriers for the delivery of small fragments of nucleic acids: oligonucleotides and siRNA. Eur J Pharm Biopharm 71:490–504

    PubMed  Google Scholar 

  187. Boussif O, Zanta MA, Behr JP (1996) Optimized galenics improve in vitro gene transfer with cationic molecules up to 1000-fold. Gene Ther 3:1074–1080

    PubMed  CAS  Google Scholar 

  188. Akinc A, Thomas M, Klibanov AM, Langer R (2005) Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. J Gene Med 7:657–663

    PubMed  CAS  Google Scholar 

  189. Grzelinski M, Urban-Klein B, Martens T, Lamszus K, Bakowsky U, Höbel S, Czubayko F, Aigner A (2006) RNA interference-mediated gene silencing of pleiotrophin through polyethylenimine-complexed small interfering RNAs in vivo exerts antitumoral effects in glioblastoma xenografts. Hum Gene Ther 17:751–766

    PubMed  CAS  Google Scholar 

  190. Akinc A, Langer R (2002) Measuring the pH environment of DNA delivered using nonviral vectors: implications for lysosomal trafficking. Biotechnol Bioeng 78:503–508

    PubMed  CAS  Google Scholar 

  191. Itaka K, Kataoka K (2009) Recent development of nonviral gene delivery systems with virus-like structures and mechanisms. Eur J Pharm Biopharm 71:475–483

    PubMed  CAS  Google Scholar 

  192. Sato A, Choi SW, Hirai M, Yamayoshi A, Moriyama R, Yamano T, Takagi M, Kano A, Shimamoto A, Maruyama A (2007) Polymer brush-stabilized polyplex for a siRNA carrier with long circulatory half-life. J Control Release 122:209–216

    PubMed  CAS  Google Scholar 

  193. Kano A, Moriyama K, Yamano T, Nakamura I, Shimada N, Maruyama A (2011) Grafting of poly(ethylene glycol) to poly-lysine augments its lifetime in blood circulation and accumulation in tumors without loss of the ability to associate with siRNA. J Control Release 149:2–7

    PubMed  CAS  Google Scholar 

  194. Merdan T, Kopecek J, Kissel T (2002) Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv Drug Deliv Rev 54:715–758

    PubMed  CAS  Google Scholar 

  195. Vaidya B, Mishra N, Dube D, Tiwari S, Vyas SP (2009) Targeted nucleic acid delivery to mitochondria. Curr Gene Ther 9:475–486

    PubMed  CAS  Google Scholar 

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  1. Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, 470003, Madhya Pradesh, India

    Shailja Tiwari, Madhu Gupta & Suresh P. Vyas

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  1. Shailja Tiwari
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  2. Madhu Gupta
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Correspondence to Suresh P. Vyas.

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Tiwari, S., Gupta, M. & Vyas, S.P. Nanocarrier Mediated Cytosolic Delivery of Drug, DNA and Proteins. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 82 (Suppl 1), 127–150 (2012). https://doi.org/10.1007/s40011-012-0078-1

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