This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

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用于选择性和有效癌症治疗的超分子纳米凝胶的氢键强度介导的自组装

该研究通过证明控制超分子聚合物内的氢键强度是定制药物递送性能和提高癌症治疗效果的关键因素，为多个氢键超分子纳米载体系统的开发做出了重大贡献。在此，我们成功开发了两种基于聚乙二醇的遥爪聚合物Cy-PEG和UrCy-PEG，它们具有自成双和四氢键胞嘧啶（Cy）和脲基胞嘧啶（UrCy）封端基团， ，它们直接组装成球形纳米凝胶，分别在水溶液中具有许多有趣的物理特性。含有四重氢键的 UrCy 二聚体的 UrCy-PEG 纳米凝胶在含血清的生物介质中表现出优异的长期结构稳定性，而双氢键的 Cy 部分不能保持 Cy-PEG 纳米凝胶的结构完整性。更重要的是，在药物包封过程之后，一系列体外实验清楚地证实，载药 UrCy-PEG 纳米凝胶在癌细胞中诱导选择性凋亡细胞死亡，而不会对健康细胞产生显着的细胞毒性，而载药 Cy-PEG 纳米凝胶对癌细胞和正常细胞均产生非选择性细胞毒性，表明增加纳米凝胶中氢键的强度在增强药物的选择性细胞摄取和细胞毒性以及随后诱导癌细胞凋亡方面起着关键作用。