The conjugation of hydrophilic polymers to proteins is an effective approach to prolonging their circulation time in the bloodstream and, hence, improving their delivery to the target region of interest. In this work, we report the synthesis of protein–polymer conjugates using a highly water-soluble sulfoxide-containing polymer, poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), through a combination of “grafting-to” and “grafting-from” methods. Oligomeric MSEA was synthesized by conventional reversible addition–fragmentation chain transfer (RAFT) polymerization and subsequently conjugated to lysozyme to produce a macromolecular chain transfer agent. This was followed by a visible light-mediated chain extension polymerization of MSEA to obtain a lysozyme–PMSEA conjugate (Lyz-PMSEA). It was found that the Lyz-PMSEA conjugate exhibited much reduced macrophage cellular uptake compared with unmodified and PEGylated lysozyme. Moreover, the Lyz-PMSEA conjugate was able to circulate longer in the bloodstream, demonstrating significantly improved pharmacokinetics demanded for pharmaceutical applications.

中文翻译：

---

与含亚砜聚合物缀合的蛋白质显示出巨噬细胞细胞摄取减少和药代动力学改善

亲水性聚合物与蛋白质的结合是延长其在血液中循环时间的有效方法，因此可以改善它们向感兴趣的目标区域的传递。在这项工作中，我们报告了使用高度水溶性的含亚砜聚合物聚（2-（甲基亚磺酰基）乙基丙烯酸酯）（PMSEA）通过“接枝”和“接枝”的组合合成蛋白质-聚合物共轭物。 - 从”方法。低聚 MSEA 通过常规的可逆加成-断裂链转移 (RAFT) 聚合合成，随后与溶菌酶缀合以产生大分子链转移剂。随后是可见光介导的 MSEA 链延长聚合，以获得溶菌酶-PMSEA 缀合物 (Lyz-PMSEA)。发现与未修饰和聚乙二醇化的溶菌酶相比，Lyz-PMSEA 缀合物表现出大大减少的巨噬细胞细胞摄取。此外，Lyz-PMSEA 偶联物能够在血液中循环更长的时间，表明药物应用所需的药代动力学显着改善。