Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Shanghai Genitourinary Cancer Institute, Shanghai, China.
Immunol Rev. 2024 Jan;321(1):181-198. doi: 10.1111/imr.13237. Epub 2023 Jul 5.
Immunogenic cell death (ICD) is a special pattern of tumor cell death, enabling to elicit tumor-specific immune response via the release of damage-associated molecular patterns and tumor-associated antigens in the tumor microenvironment. ICD-induced immunotherapy holds the promise for completely eliminating tumors and long-term protective antitumor immune response. Increasing ICD inducers have been discovered for boosting antitumor immunity via evoking ICD. Nonetheless, the utilization of ICD inducers remains insufficient owing to serious toxic reactions, low localization efficiency within the tumor microenvironmental niche, etc. For overcoming such limitations, stimuli-responsive multifunctional nanoparticles or nanocomposites with ICD inducers have been developed for improving immunotherapeutic efficiency via lowering toxicity, which represent a prospective scheme for fostering the utilization of ICD inducers in immunotherapy. This review outlines the advances in near-infrared (NIR)-, pH-, redox-, pH- and redox-, or NIR- and tumor microenvironment-responsive nanodelivery systems for ICD induction. Furthermore, we discuss their clinical translational potential. The progress of stimuli-responsive nanoparticles in clinical settings depends upon the development of biologically safer drugs tailored to patient needs. Moreover, an in-depth comprehending of ICD biomarkers, immunosuppressive microenvironment, and ICD inducers may accelerate the advance in smarter multifunctional nanodelivery systems to further amplify ICD.
免疫原性细胞死亡（ICD）是一种特殊的肿瘤细胞死亡模式，通过在肿瘤微环境中释放损伤相关分子模式和肿瘤相关抗原，能够引发肿瘤特异性免疫反应。ICD 诱导的免疫疗法有望彻底消除肿瘤并产生长期的保护性抗肿瘤免疫反应。为了增强抗肿瘤免疫，已经发现了越来越多的 ICD 诱导剂来诱导 ICD。然而，由于严重的毒副作用、在肿瘤微环境龛内的定位效率低等原因，ICD 诱导剂的应用仍然不足。为了克服这些限制，已经开发了具有 ICD 诱导剂的刺激响应多功能纳米粒子或纳米复合材料，通过降低毒性来提高免疫治疗效率，这代表了促进 ICD 诱导剂在免疫治疗中应用的一种有前景的方案。本文概述了近红外（NIR）、pH、氧化还原、pH 和氧化还原、或 NIR 和肿瘤微环境响应的纳米递药系统在 ICD 诱导方面的进展。此外，我们还讨论了它们的临床转化潜力。刺激响应型纳米粒子在临床环境中的进展取决于针对患者需求定制的更安全的生物药物的开发。此外，深入了解 ICD 生物标志物、免疫抑制微环境和 ICD 诱导剂，可能会加速更智能的多功能纳米递药系统的进展，以进一步放大 ICD。
