Stimuli-responsive prodrug-based nanoplatform with synergistic antitumor activity is of central importance to the development of promising nanomedicines for cancer therapy. Here, we describe a polydopamine-drug conjugate nanocomposite (ZP-PDA-DOX) with targeted cancer photothermal-chemotherapy (PTT-CT), which constructed by a gradual copolymerization of dopamine (DA) and pH-sensitive dopamine-derived prodrug (DA-DOX) into the porous channels of zeolite imidazolate frameworks-8 (ZIF-8), followed by PEGylation with amino-terminated folic acid-polyethylene glycol (NH₂-PEG-FA) to acquire the high biocompatibility, specificity, and excellent tumor-targeting property. The incorporation of polydopamine strengthened the stability and dispersion of ZIF-8, and also conferred photothermal conversion effect. In the tumor acidic microenvironment, the acid-labile hydrazone linker of DA-DOX and ZIF-8 promptly degraded to release activated DOX. Moreover, the generated hyperthermia due to the high photothermal conversion efficiency of PDA component could accelerate drug release, and simultaneously thermally ablate tumor tissue to maximize the DOX-induced CT, which could also assist PTT to eradicate tumor cells. This study provides a promising strategy for targeted cancer PTT-CT with synergistic anti-tumor effect.

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基于 ZIF-8 的聚多巴胺-药物共轭纳米复合材料用于靶向癌症光热化疗

具有协同抗肿瘤活性的刺激响应性前药纳米平台对于开发用于癌症治疗的有前景的纳米药物至关重要。在这里，我们描述了一种具有靶向癌症光热化疗 (PTT-CT) 的聚多巴胺-药物共轭纳米复合材料 (ZP-PDA-DOX)，它由多巴胺 (DA) 和 pH 敏感的多巴胺衍生前药 (DA) 逐渐共聚而成。 -DOX) 进入沸石咪唑酯骨架 8 (ZIF-8) 的多孔通道，然后用端氨基叶酸-聚乙二醇 (NH _{2 ) 进行 PEG 化}-PEG-FA) 获得高生物相容性、特异性和优异的肿瘤靶向性。聚多巴胺的加入增强了 ZIF-8 的稳定性和分散性，同时也赋予了光热转换效应。在肿瘤酸性微环境中，DA-DOX 和 ZIF-8 的酸不稳定腙接头迅速降解释放活化的 DOX。此外，由于 PDA 成分的高光热转换效率而产生的热疗可以加速药物释放，同时热消融肿瘤组织以最大化 DOX 诱导的 CT，这也可以帮助 PTT 根除肿瘤细胞。该研究为具有协同抗肿瘤作用的靶向癌症PTT-CT提供了一种有前景的策略。