Immunotherapy displays potent potential for clinical cancer management by activating the protective immune response; however, the microenvironment of the immunosuppressive tumor restricts the efficiency of immunotherapies. Along with the complex pathophysiological barrier of the solid tumors, successful immunotherapeutic delivery remains a formidable challenge for conventional nanomedicine. Stimuli-sheddable nano vectors may facilitate the delivery of cargoes to tumors with minimal premature cargo leakage in blood circulation while enhancing the tumor penetration of nanomedicines by deshielding the polyethylene glycol (PEG) corona upon endogenous activity such as acidity, enzymes and glutathione, or external stimuli, such as laser irradiation. Throughout this study, researchers overviewed the recent advances of nanomedicine-based cancer immunotherapy using the stimuli-responsive deshielding nano vectors, which allowed researchers to integrate multiple therapeutic regimens for inducing immunogenic cell death. This aided in blocking the immune checkpoints, repolarizing the macrophages, and regulating the kynurenine metabolism. Furthermore, researchers discussed the critical issues in the development of stimuli-sheddable nanoimmunodulators, primarily aimed at speeding up their clinical translation. Finally, researchers provided novel perspectives for improving cancer management with the stimuli-sheddable nanomedicine.

中文翻译：

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可刺激脱落的纳米医学克服病理生理学障碍以增强癌症的免疫治疗。

免疫疗法通过激活保护性免疫反应显示出临床癌症管理的强大潜力；然而，免疫抑制性肿瘤的微环境限制了免疫治疗的效率。除了实体瘤的复杂病理生理屏障外，成功的免疫治疗递送仍然是传统纳米医学的一项艰巨挑战。可刺激脱落的纳米载体可以促进将货物输送到肿瘤，同时最大限度地减少血液循环中过早的货物泄漏，同时通过对聚乙二醇 (PEG) 电晕的内源性活性（如酸度、酶和谷胱甘肽）或外部活性进行去屏蔽来增强纳米药物的肿瘤渗透刺激，如激光照射。在整个研究过程中，研究人员概述了使用刺激响应去屏蔽纳米载体的基于纳米医学的癌症免疫疗法的最新进展，这使研究人员能够整合多种治疗方案来诱导免疫原性细胞死亡。这有助于阻断​​免疫检查点，使巨噬细胞重新极化，并调节犬尿氨酸代谢。此外，研究人员讨论了可刺激脱落纳米免疫调节剂开发中的关键问题，主要旨在加快其临床转化。最后，研究人员为利用可刺激脱落的纳米药物改善癌症管理提供了新的视角。这有助于阻断​​免疫检查点，使巨噬细胞重新极化，并调节犬尿氨酸代谢。此外，研究人员讨论了可刺激脱落纳米免疫调节剂开发中的关键问题，主要旨在加快其临床转化。最后，研究人员为利用可刺激脱落的纳米药物改善癌症管理提供了新的视角。这有助于阻断​​免疫检查点，使巨噬细胞重新极化，并调节犬尿氨酸代谢。此外，研究人员讨论了可刺激脱落纳米免疫调节剂开发中的关键问题，主要旨在加快其临床转化。最后，研究人员为利用可刺激脱落的纳米药物改善癌症管理提供了新的视角。