Abstract
Engineered PEG-cleavable catiomers based on poly-l-lysine have been developed as nonviral gene vectors, which have been found to be one of important methods to balance “PEG dilemma.” In this protocol, we aim at the standardization of the method and procedure of PEG-cleavable catiomers. Major steps including ring-opening polymerization (ROP) of ε-benzyloxycarbonyl-l-lysine N-carboxyanhydride (zLL-NCA) monomers to yield PEG-cleavable polylysine, examination on bio-stability and bio-efficacy of its gene complexes are described.
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References
Toncheva V, Wolfert MA, Dash PR, Oupicky D, Ulbrich K, Seymour LW, Schacht EH (1998) Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers. Biochim Biophys Acta 1380:354–368
Rungsardthong U, Deshpande M, Bailey L, Vamvakaki M, Armes SP, Garnett MC, Stolnik S (2001) Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene therapy. J Control Release 73:359–380
Mannisto M, Vanderkerken S, Toncheva V, Elomaa M, Ruponen M, Schacht E, Urtti A (2002) Structure-activity relationships of poly(L-lysines): effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery. J Control Release 83:169–182
Langer R (1998) Drug delivery and targeting. Nature 392:5–10
Otsuka H, Nagasaki Y, Kataoka K (2003) PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev 55:403–419
Riehemann K, Schneider SW, Luger TA, Godin B, Ferrari M, Fuchs H (2009) Nanomedicine—challenge and perspectives. Angew Chem Int Ed Engl 48:872–897
Knop K, Hoogenboom R, Fischer D, Schubert US (2010) Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed Engl 49:6288–6308
Masuda T, Akita H, Niikura K, Nishio T, Ukawa M, Enoto K, Danev R, Nagayama K, Ijiro K, Harashima H (2009) Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription. Biomaterials 30:4806–4814
Nie S (2010) Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine (Lond) 5:523–528
Pozzi D, Colapicchioni V, Caracciolo G, Piovesana S, Capriotti AL, Palchetti S, De Grossi S, Riccioli A, Amenitsch H, Lagana A (2014) Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells. Nanoscale 6:2782–2792
Lin S, Du F, Wang Y, Ji S, Liang D, Yu L, Li Z (2008) An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems. Biomacromolecules 9:109–115
Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H (2009) A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. J Control Release 139:127–132
Cai X, Dong C, Dong H, Wang G, Pauletti GM, Pan X, Wen H, Mehl I, Li Y, Shi D (2012) Effective gene delivery using stimulus-responsive catiomer designed with redox-sensitive disulfide and acid-labile imine linkers. Biomacromolecules 13:1024–1034
Wang K, Liu Y, Yi WJ, Li C, Li YY, Zhuo RX, Zhang XZ (2013) Novel shell-cross-linked micelles with detachable PEG corona for glutathione-mediated intracellular drug delivery. Soft Matter 9:692–699
Zhu H, Dong C, Dong H, Ren T, Wen X, Su J, Li Y (2014) Cleavable PEGylation and hydrophobic histidylation of polylysine for siRNA delivery and tumor gene therapy. ACS Appl Mater Interfaces 6:10393–10407
Son S, Namgung R, Kim J, Singha K, Kim WJ (2012) Bioreducible polymers for gene silencing and delivery. Acc Chem Res 45:1100–1112
van Gaal EV, van Eijk R, Oosting RS, Kok RJ, Hennink WE, Crommelin DJ, Mastrobattista E (2011) How to screen non-viral gene delivery systems in vitro? J Control Release 154:218–232
Cai XJ, Dong HQ, Xia WJ, Wen HY, Li XQ, Yu JH, Li YY, Shi DL (2011) Glutathione-mediated shedding of PEG layers based on disulfide-linked catiomers for DNA delivery. J Mater Chem 21:14639–14645
Acknowledgement
This work was financially supported by research grants from the National Natural Science Foundation of China (NSFC 21104059 and 51173136), the Fundamental Research Funds for the Central Universities (2013KJ038), and “Chen Guang” project (12CG17) founded by Shanghai Municipal Education Commission and Shanghai Education Development Foundation.
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Tang, M., Dong, H., Cai, X., Zhu, H., Ren, T., Li, Y. (2016). Disulfide-Bridged Cleavable PEGylation of Poly-l-Lysine for SiRNA Delivery. In: Shum, K., Rossi, J. (eds) SiRNA Delivery Methods. Methods in Molecular Biology, vol 1364. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3112-5_5
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DOI: https://doi.org/10.1007/978-1-4939-3112-5_5
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3111-8
Online ISBN: 978-1-4939-3112-5
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