PEGylation, covalent attachment of PEG to therapeutic biomolecules, in which suboptimal pharmacokinetic profiles limiting their therapeutic utility are of concern, is a widely applied technology. However, this technology has been challenged by reduced bioactivity of biomolecules upon PEGylation and immunogenicity of PEG triggering immune response and abrogating clinical efficacy, which collectively necessitate development of stealth polymer alternatives. Here we demonstrate that comb-shape poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA), a stealth polymer alternative, has a more compact structure than PEG and self-organize into nanoparticles in a molecular weight dependent manner. Most notably, we show that comb-shape POEGMA promotes significantly higher cellular uptake and exhibits less steric hindrance imposed on the conjugated biomolecule than PEG. Collectively, comb-shape POEGMA offers a versatile alternative to PEG for stealth polymer–biomolecule conjugation applications.

中文翻译：

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分子结构对PEG细胞相互作用和隐身特性的影响

聚乙二醇化（PEG与治疗性生物分子的共价连接）是一种广泛应用的技术，其中限制了其治疗效用的次佳药物代谢动力学特征值得关注。但是，这项技术受到了聚乙二醇化后生物分子生物活性降低的挑战，而PEG的免疫原性触发了免疫反应并废除了临床功效，这共同要求开发隐形聚合物替代品。在这里，我们证明了一种隐型聚合物替代品-梳型聚[乙二醇（甲基）甲基醚甲基丙烯酸甲酯]（POEGMA），具有比PEG更紧凑的结构，并以分子量依赖的方式自组装成纳米颗粒。最为显着地，我们显示，梳形POEGMA促进了明显更高的细胞摄取，并表现出比PEG更少的施加在共轭生物分子上的空间位阻。总的来说，梳形POEGMA为隐身聚合物-生物分子偶联应用提供了PEG的通用替代品。