Liu Changling, Wang Yirong, Wang Siyu, Xu Pengcheng, Liu Renning, Han Dandan, Wei Yen
School of Materials Science and Engineering, Jilin Institute of Chemical Technology, Jilin City 132022, China.
College of Biology and Food Engineering, Jilin Institute of Chemical Technology, Jilin City 132022, China.
Polymers (Basel). 2023 Jan 18;15(3):509. doi: 10.3390/polym15030509.
The novel thermosensitive star-shaped tetra-hydroxy-phenylporphyrin-cored (THPP) double hydrophilic poly(N-isopropylacrylamide)-b-poly(methylacrylamide glucose) block copolymers (THPP-(PNIPAM--PMAGA)) were synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization. Notably, the low critical solution temperatures (LCSTs) of THPP-(PNIPAM--PMAGA) were above normal body temperature (37 °C) which depended on the hydrophilic PMAGA contents of copolymers. When the temperature was higher than the LCST of the copolymer, the copolymer could be neutralized into micelles in aqueous and could be coated with antitumor drugs and released around tumor cells. The MTT study indicated that THPP-(PNIPAM--PMAGA) had a low toxicity to L929 and HeLa cells in the absence of light. However, THPP-(PNIPAM--PMAGA) showed a high toxicity with HeLa cells under light irradiation which could be used as a potential photosensitizer for photodynamic therapy (PDT). In addition, THPP-(PNIPAM--PMAGA) showed specific a recognition function with Concanavalin A (Con A) to achieve active targeted drug delivery. This work provides a new approach for the development of tumor targeting and chemotherapy/PDT.
通过可逆加成-断裂链转移（RAFT）聚合反应合成了新型的以热敏性星形四羟基苯基卟啉（THPP）为核的双亲水聚（N-异丙基丙烯酰胺）-b-聚（甲基丙烯酰胺葡萄糖）嵌段共聚物（THPP-(PNIPAM-b-PMAGA)）。值得注意的是，THPP-(PNIPAM-b-PMAGA)的低临界溶液温度（LCST）高于正常体温（37℃），这取决于共聚物中亲水的PMAGA含量。当温度高于共聚物的LCST时，共聚物在水溶液中可形成胶束，并可负载抗肿瘤药物并在肿瘤细胞周围释放。MTT研究表明，在无光条件下，THPP-(PNIPAM-b-PMAGA)对L929和HeLa细胞的毒性较低。然而，THPP-(PNIPAM-b-PMAGA)在光照下对HeLa细胞表现出高毒性，可作为光动力疗法（PDT）的潜在光敏剂。此外，THPP-(PNIPAM-b-PMAGA)对伴刀豆球蛋白A（Con A）具有特异性识别功能，可实现主动靶向给药。这项工作为肿瘤靶向及化疗/光动力治疗的发展提供了一种新方法。
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