Precisely targeted gene delivery in human skin using supramolecular cationic glycopolymers
Precisely targeted gene delivery in human skin using supramolecular cationic glycopolymers
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DOI：
10.1039/d0py00449a
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发表时间：
2020-06-14
影响因子：
4.6
通讯作者：
Becer, C. Remzi
中科院分区：
文献类型：
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作者：
Blakney, Anna K.;Liu, Renjie;Becer, C. Remzi
基因递送已成为临床治疗的焦点，从而激发了能够在疫苗和治疗剂的背景下靶向某些细胞类型的递送策略。在这里，我们提出了一个基因传递平台，使主客体之间的相互作用的环糊精与散发链的阳离子聚合物，聚（2-二甲基氨基乙基甲基丙烯酸酯）（PDMAEMA）配对的糖基化的金刚烷含共聚物。通过将阳离子聚合物和糖基化化学反应解耦，我们能够独立地改变每一种以研究体外和人皮肤外植体中的转染效率。中等长度的PDMAEMA能够实现最佳的DNA复合，并且糖基化特异性地增加了体外100倍折叠和体内3倍折叠转染的细胞数量。此外，这些糖聚合物使更大的免疫细胞摄取，特别是在皮肤驻留的白细胞。该平台是研究糖基化如何影响复杂细胞介质中的细胞摄取和靶向的一种简便且临床上可转化的方法。
Gene delivery has become the focus of clinical treatments, thus motivating delivery strategies that are capable of targeting certain cell types in the context of both vaccines and therapeutics. Here, we present a gene delivery platform enabled by host-guest interaction between a cyclodextrin with emanating chains of cationic polymers, poly(2-dimethylaminoethyl meth-acrylate) (PDMAEMA) paired with a glycosylated adamantane containing copolymer. By decoupling the cationic polymer and glycosylation chemistries, we were able to vary each independently to study the transfection efficiency bothin vitroandex vivoin human skin explants. Medium length PDMAEMA enabled optimal DNA complexation, and glycosylation specifically enhanced the number of cells transfected 100-foldin vitroand 3-foldex vivo. Furthermore, these glycopolymers enabled greater immune cell up take, specifically in skin resident leukocytes. This platform is a facile and clinically translatable way to study how glycosylation affects cellular uptake and targeting in a complex cellular medium.