School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China.
Hebei Key Laboratory of Functional Polymers, Tianjin 300130, China.
Biomacromolecules. 2023 May 8;24(5):1994-2002. doi: 10.1021/acs.biomac.2c01368. Epub 2023 Apr 1.
To fabricate nanoscale proteinosomes, thermoresponsive miktoarm polymer protein bioconjugates were prepared through highly efficient molecular recognition between the β-cyclodextrin modified BSA (CD-BSA) and the adamantyl group anchored at the junction point of the thermoresponsive block copolymer poly(ethylene glycol)--poly(di(ethylene glycol) methyl ether methacrylate) (PEG--PDEGMA). PEG--PDEGMA was synthesized by the Passerini reaction of benzaldehyde-modified PEG, 2-bromo-2-methylpropionic acid, and 1-isocyanoadamantane, followed by the atom transfer radical polymerization of DEGMA. Two block copolymers with different chain lengths of PDEGMA were prepared, and both self-assembled into polymersomes at a temperature above their lower critical solution temperatures (LCST). The two copolymers can undergo molecular recognition with the CD-BSA and form miktoarm star-like bioconjugates. The bioconjugates self-assembled into ∼160 nm proteinosomes at a temperature above their LCSTs, and the miktoarm star-like structure has a great effect on the formation of the proteinosomes. Most of the secondary structure and esterase activity of BSA in the proteinosomes were maintained. The proteinosomes exhibited low toxicity to the 4T1 cells and could deliver model drug doxorubicin into the 4T1 cells.
为了制备纳米级蛋白质体，通过β-环糊精修饰的牛血清白蛋白（CD-BSA）与接枝在温敏嵌段共聚物聚乙二醇-聚（二乙二醇甲基醚甲基丙烯酸酯）（PEG-PDEGMA）连接点上的金刚烷基团之间的高效分子识别，制备了温敏多臂聚合物蛋白生物缀合物。PEG-PDEGMA 通过苯甲醛修饰的 PEG、2-溴-2-甲基丙酸和 1-异氰基金刚烷的 Passerini 反应，然后通过 DEGMA 的原子转移自由基聚合合成。合成了两种具有不同 PDEGMA 链长的嵌段共聚物，它们在高于其低临界溶液温度（LCST）的温度下自组装成聚合物体。这两种共聚物可以与 CD-BSA 进行分子识别，并形成多臂星状生物缀合物。在高于其 LCST 的温度下，生物缀合物自组装成约 160nm 的蛋白质体，并且多臂星状结构对蛋白质体的形成有很大的影响。蛋白质体中的 BSA 的大部分二级结构和酯酶活性得以保持。蛋白质体对 4T1 细胞的毒性较低，并可以将模型药物阿霉素递送到 4T1 细胞中。
