Main-chain degradable single-chain cyclized polymers as gene delivery vectors

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• 作者：Yongsheng Gao^a ; ¹ ; Verena I. Bö ; hmer^a ; ^b ; ¹ ; ² ; Dezhong Zhou^a ; Tianyu Zhao^a ; Wenxin Wang^a ; ^{wenxin.wang@ucd.ie} ; Jos M.J. Paulusse^b ; ^c ; ^{j.m.j.paulusse@utwente.nl}
• 关键词：Single chain technology ; Radical ring opening polymerization ; Degradability ; Polymer nanoparticles ; Gene delivery
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 December 2016
• 年：2016
• 卷：244
• 期：part_PB
• 页码：375-383
• 全文大小：1125 K
• 卷排序：244

文摘

Single-chain technology (SCT) allows the manipulation of polymeric architectures at an individual polymer chain level, providing a new platform for the fabrication of nanoscale polymeric objects. However, it remains problematic to apply this newborn technology to the biological and medical fields, since synthesis of single-chain polymeric nanoparticles relies heavily on controlled/living radical polymerization of vinyl based monomers, yielding a persistent non-degradable carbon-carbon based backbone. Moreover, the ultrahigh dilution conditions often required for single-chain polymer nanoparticle synthesis limits large-scale applicability. A versatile approach to achieve backbone degradability in single-chain cyclized polymers was developed by combining ring-opening addition polymerization and intramolecular cyclization into a one-pot RAFT copolymerization of cyclic and mono/multi-vinyl monomers system under concentrated conditions. The in situ intramolecular cyclization of individual propagating chains was achieved by kinetic control and statistical manipulation of mono- and multi-vinyl monomer copolymerization. The cyclic allylsulfide monomer 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MDTD) was copolymerized via the ring-opening pathway to introduce disulfide groups into the vinyl-based backbone without compromising the single chain propagation nature. Backbone degradable single chain polymeric nanoparticles were obtained with molecular weights of 10 kDa and MDTD incorporation ratios of 4.7%. Chemical degradation of the nanoparticles confirmed both their single chain nature, as well as backbone degradability. The single-chain cyclized polymeric nanoparticles were evaluated for their gene transfection capabilities. The backbone degradable nanoparticles displayed high transfection efficiencies and low cytotoxicities in both 3T3 and HeLa cells.