Immunotherapy has shifted the clinical paradigm of cancer management. However, despite promising initial progress, immunotherapeutic approaches to cancer still suffer from relatively low response rates and the possibility of severe side effects, likely due to the low inherent immunogenicity of tumor cells, the immunosuppressive tumor microenvironment, and significant inter‐ and intratumoral heterogeneity. Recently, nanoformulations of prodrugs have been explored as a means to enhance cancer immunotherapy by simultaneously eliciting antitumor immune responses and reversing local immunosuppression. Prodrug nanomedicines, which integrate engineering advances in chemistry, oncoimmunology, and material science, are rationally designed through chemically modifying small molecule drugs, peptides, or antibodies to yield increased bioavailability and spatiotemporal control of drug release and activation at the target sites. Such strategies can help reduce adverse effects and enable codelivery of multiple immune modulators to yield synergistic cancer immunotherapy. In this review article, recent advances and translational challenges facing prodrug nanomedicines for cancer immunotherapy are overviewed. Last, key considerations are outlined for future efforts to advance prodrug nanomedicines aimed to improve antitumor immune responses and combat immune tolerogenic microenvironments.

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用于癌症免疫治疗的工程前药纳米药物

免疫疗法改变了癌症治疗的临床模式。然而，尽管取得了初步进展，癌症免疫治疗方法仍然存在相对较低的反应率和可能出现严重副作用的问题，这可能是由于肿瘤细胞固有的免疫原性低、免疫抑制性肿瘤微环境以及显着的肿瘤间和肿瘤内异质性所致。最近，前药纳米制剂已被探索作为一种通过同时引发抗肿瘤免疫反应和逆转局部免疫抑制来增强癌症免疫治疗的手段。前药纳米药物融合了化学、肿瘤免疫学和材料科学方面的工程进展，通过对小分子药物、肽或抗体进行化学修饰来合理设计，以提高生物利用度以及对靶位点药物释放和激活的时空控制。这些策略可以帮助减少不良反应，并使多种免疫调节剂同时给药，从而产生协同的癌症免疫疗法。在这篇综述文章中，概述了用于癌症免疫治疗的前药纳米药物的最新进展和转化挑战。最后，概述了未来努力推进前药纳米药物的关键考虑因素，旨在改善抗肿瘤免疫反应和对抗免疫耐受性微环境。