College of Chemistry and Chemical Engineering, Inner Magnolia University, Huhhot, 010021, China.
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
J Biomed Nanotechnol. 2021 Aug 1;17(8):1486-1509. doi: 10.1166/jbn.2021.3134.
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.
免疫疗法通过激活保护性免疫反应显示出在癌症临床治疗中的巨大潜力；然而，免疫抑制肿瘤的微环境限制了免疫疗法的效率。与实体瘤复杂的病理生理障碍一起，传统的纳米医学在成功进行免疫治疗输送方面仍然面临巨大挑战。刺激响应性纳米载体可促进将药物输送至肿瘤，同时最小化药物在血液循环中的早期泄漏，并且通过在酸性、酶和谷胱甘肽等内源性活性或激光照射等外部刺激下，屏蔽聚乙二醇（PEG）冠，增强纳米药物对肿瘤的穿透性。在这项研究中，研究人员综述了基于纳米医学的癌症免疫治疗中使用刺激响应性去屏蔽纳米载体的最新进展，这使得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、重新极化巨噬细胞并调节犬尿氨酸代谢。此外，研究人员还讨论了刺激响应性纳米免疫调节剂发展中的关键问题，主要目的是加速其临床转化。最后，研究人员为使用刺激响应性纳米医学改善癌症治疗提供了新的视角。
