Zwitterionic polymers with high biocompatibility and extremely low fouling properties have attracted interest as promising nanocarriers for drug delivery. In this work, novel zwitterionic nano-gels were prepared via the facile one-pot “click” reaction of α, ω-functionalized poly(sulfobetaine)s (FPSBs) and cystamine. FPSBs were first synthesized by atom transfer radical polymerization with initiators having furan-maleimide adducts followed by the end-capping reaction with thiolactone derivatives. Subsequently, the thiolactone rings of PSBs could be opened by aminolysis of cystamine crosslinkers and the released thiol-groups reacted with the double-bonds of furan-maleimide moieties to form PSB nanogel networks through the thiol-ene “click” reaction. The nanogels were readily degraded in the presence of glutathione (GSH) as a reducing agent, which was confirmed by the changes in particle size. Doxorubicin (DOX), could be loaded in the core of the nanogels with a high drug loading content of 24.3%. Moreover, the in vitro drug release profile showed a low release (24.8%) of DOX at a physiological environment, whereas there were burst releases of 74.4% and 89.9% in the presence of 5 mM and 10 mM GSH similar to a tumor cytoplasm environment. Cell viability assays demonstrated that the nanogel showed low cytotoxicity against the normal HEK293 cell, while exhibited a high cytotoxic activity towards HeLa cancer cells. These evidences revealed the effective redox responsive characteristics of the PSB nanogels.

具有高生物相容性和极低结垢特性的两性离子聚合物作为有前景的用于药物递送的纳米载体引起了人们的兴趣。在这项工作中，通过α，ω-官能化的聚（磺基甜菜碱）（FPSB）和胱胺的一键式“点击”反应制备了新型的两性离子纳米凝胶。首先通过具有呋喃-马来酰亚胺加合物的引发剂通过原子转移自由基聚合，然后与硫代内酯衍生物进行封端反应，来合成FPSB。随后，可以通过胱胺交联剂的氨解来打开PSB的硫内酯环，释放的硫醇基团与呋喃-马来酰亚胺部分的双键反应，通过硫醇-烯“点击”反应形成PSB纳米凝胶网络。在存在作为还原剂的谷胱甘肽（GSH）的情况下，纳米凝胶易于降解，粒径变化证实了这一点。阿霉素（DOX）可以以24.3％的高载药量负载在纳米凝胶的核心中。此外，体外药物释放曲线显示在生理环境下DOX的释放较低（24.8％），而在类似于肿瘤细胞质环境的5 mM和10 mM GSH的存在下有74.4％和89.9％的突释释放。细胞活力测定表明，纳米凝胶对正常的HEK293细胞显示出低细胞毒性，而对HeLa癌细胞则显示出高细胞毒性活性。这些证据揭示了PSB纳米凝胶的有效氧化还原响应特性。体外药物释放曲线显示，在生理环境下，DOX的释放率较低（24.8％），而在5 mM和10 mM GSH的存在下，类似于肿瘤细胞质环境下的突释释放分别为74.4％和89.9％。细胞活力测定表明，纳米凝胶对正常的HEK293细胞显示出低细胞毒性，而对HeLa癌细胞则显示出高细胞毒性活性。这些证据揭示了PSB纳米凝胶的有效氧化还原响应特性。体外药物释放曲线显示，在生理环境下，DOX的释放率较低（24.8％），而在5 mM和10 mM GSH的存在下，类似于肿瘤细胞质环境下的突释释放分别为74.4％和89.9％。细胞活力测定表明，纳米凝胶对正常的HEK293细胞显示出低细胞毒性，而对HeLa癌细胞则显示出高细胞毒性活性。这些证据揭示了PSB纳米凝胶的有效氧化还原响应特性。而对HeLa癌细胞则表现出很高的细胞毒活性。这些证据揭示了PSB纳米凝胶的有效氧化还原响应特性。而对HeLa癌细胞则表现出很高的细胞毒活性。这些证据揭示了PSB纳米凝胶的有效氧化还原响应特性。