Prodrug nanoassemblies are emerging as a novel drug delivery system for chemotherapy, comprising four fundamental modules: a drug module, a modification module, a response module, and a surface functionalization module. Among these modules, surface functionalization is an essential process to enhance the biocompatibility and stability of the nanoassemblies. Here, we selected mitoxantrone (MTO) as the drug module and DSPE-PEG_2K as surface functionalization module to develop MTO prodrug nanoassemblies. We systematically evaluated the effect of surface functionalization module ratios (10%, 20%, 40%, and 60% of prodrug, W_{DSPE-mPEG2000}/W_prodrug) on the prodrug nanoassemblies. The results indicated that 40% NPs significantly improved the self-assembly stability and cellular uptake of prodrug nanoassemblies. Compared with MTO solution, 40% NPs showed better tumor specificity and pharmacokinetics, resulting in potent antitumor activity with a good safety profile. These findings highlighted the pivotal role of the surface functionalization module in regulating the performance of mitoxantrone prodrug nanoassemblies for cancer treatment.

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探讨表面功能化模块对米托蒽醌前药纳米组件性能的影响：提高有效性和安全性

前药纳米组件正在成为一种新型的化疗药物递送系统，包括四个基本模块：药物模块、修饰模块、响应模块和表面功能化模块。在这些模块中，表面功能化是增强纳米组件的生物相容性和稳定性的重要过程。在这里，我们选择米托蒽醌（MTO）作为药物模块，DSPE-PEG _2K作为表面功能化模块来开发MTO前药纳米组件。我们系统地评估了表面功能化模块比例（前药的 10%、20%、40% 和 60%，W _{DSPE-mPEG2000} / W_前药）对前药纳米组件的影响。结果表明，40% NPs 显着提高了前药纳米组装体的自组装稳定性和细胞摄取。与 MTO 溶液相比，40% NPs 显示出更好的肿瘤特异性和药代动力学，从而具有有效的抗肿瘤活性和良好的安全性。这些发现强调了表面功能化模块在调节米托蒽醌前药纳米组件用于癌症治疗的性能中的关键作用。