Li Hao, Li Xian, Zhang Chao, Sun Qiquan, Yi Wei, Wang Xuan, Cheng Du, Chen Shupeng, Liang Biling, Shuai Xintao
J Biomed Nanotechnol. 2016 Jun;12(6):1258-69. doi: 10.1166/jbn.2016.2247.
A diblock copolymer of poly(ethylene glycol) (PEG) and poly(γ-benzyl L-glutamate) (PBLG), PEG-PBLG, was synthesized via the ring-opening polymerization of γ-benzyl L-glutamate N-carboxyanhydride (BLG-NCA) using allyl-PEG-NH2 as a macroinitiator. After deprotection of the benzyl groups, N,N-diisopropyl ethylenediamine (DIP) was conjugated to poly(L-glutamic acid) (PGA) blocks as side groups. The pendant DIP groups on the PGA blocks greatly enhance the pH-sensitivity of poly(ethylene glycol)-block-poly[N-(N',N'-diisopropylaminoethyl) glutamide] [PEG-PGA(DIP)] micelles, and a higher grafting percentage of DIP favors a faster acid-response. In neutral aqueous solution, the PEG-PGA(DIP) can self-assemble into stable micelles featuring an acid-responsive PGA(DIP) core with the encapsulated anticancer drug doxorubicin (DOX). In an acidic environment, the hydrophobic-hydrophilic transition of the PGA block leads to the gradual expansion and disassembly of these micelles and, consequently, an accelerated release of DOX. Thus, DOX transported by PEG-PGA(DIP) micelles can be entrapped more efficiently into the nuclei of hepatoma Bel 7402 cells.
聚乙二醇（PEG）与聚（γ-苄基-L-谷氨酸）（PBLG）的二嵌段共聚物PEG-PBLG，通过使用烯丙基-PEG-NH2作为大分子引发剂，使γ-苄基-L-谷氨酸N-羧基环酐（BLG-NCA）进行开环聚合反应合成。苄基脱保护后，将N，N-二异丙基乙二胺（DIP）作为侧基连接到聚（L-谷氨酸）（PGA）嵌段上。PGA嵌段上的侧挂DIP基团极大地增强了聚乙二醇-嵌段-聚[N-（N'，N'-二异丙基氨基乙基）谷氨酰胺][PEG-PGA（DIP）]胶束的pH敏感性，并且DIP的较高接枝率有利于更快的酸响应。在中性水溶液中，PEG-PGA（DIP）可以自组装成稳定的胶束，其具有包裹抗癌药物阿霉素（DOX）的酸响应性PGA（DIP）核。在酸性环境中，PGA嵌段的疏水-亲水转变导致这些胶束逐渐膨胀和解体，从而加速DOX的释放。因此，由PEG-PGA（DIP）胶束转运的DOX可以更有效地被捕获到肝癌Bel 7402细胞的细胞核中。
