Abstract：
Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.
摘要：
前药纳米组装体结合了前药策略和纳米技术的优点，已被广泛用于递送抗肿瘤药物。这些前药通常包含活性药物模块，响应模块，和修改模块。其中,修饰模块是提高母体药物自组装能力的关键因素。然而,修饰模块的特定结构对前药自组装的影响仍然难以捉摸。在这项研究中,使用2-辛基-1-十二烷醇(OD)作为柔性修饰模块和胆固醇(CLS)作为刚性修饰模块开发了两种吉西他滨(GEM)前药。有趣的是,改性模块化学结构的差异显著影响组装性能,药物释放，细胞毒性，肿瘤积聚，前药纳米组装体的抗肿瘤功效。值得注意的是，用柔性修饰链（OD）构建的前药纳米组装体显示出改善的稳定性，更快的药物释放，和增强的抗肿瘤作用。我们的发现阐明了修饰模块对前药纳米组装体构建的重要影响。
