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用于癌症化学动力学治疗与免疫治疗联合的纳米医学。

Nanomedicine for combination of chemodynamic therapy and immunotherapy of cancers.

机构信息

School of Chemistry, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, China.

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, China.

出版信息

Biomater Sci. 2024 Sep 10;12(18):4607-4629. doi: 10.1039/d3bm02133e.

Abstract

Chemodynamic therapy (CDT), as a new type of therapy, has received more and more attention in the field of tumor therapy in recent years. By virtue of the characteristics of weak acidity and excess HO in the tumor microenvironment, CDT uses the Fenton or Fenton-like reactions to catalyze the transformation of HO into strongly oxidizing ˙OH, resulting in increased intracellular oxidative stress for lipid oxidation, protein inactivation, or DNA damage, and finally inducing apoptosis of cancer cells. In particular, CDT has the advantage of tumor specificity. However, the therapeutic efficacy of CDT frequently depends on the catalytic efficiency of the Fenton reaction, which needs the presence of sufficient HO and catalytic metal ions. Relatively low concentrations of HO and the lack of catalytic metal ions usually limit the final therapeutic effect. The combination of CDT with immunotherapy will be an effective means to improve the therapeutic effect. In this review paper, the recent progress related to nanomedicine for the combination of CDT and immunotherapy is summarized. Immunogenic death of tumor cells, immune checkpoint inhibitors, and stimulator of interferon gene (STING) activation as the main immunotherapy strategies to combine with CDT are discussed. Finally, the challenges and prospects for the clinical translation and future development direction are discussed.

摘要

化学动力学疗法(CDT)作为一种新型疗法,近年来在肿瘤治疗领域受到越来越多的关注。CDT 利用肿瘤微环境的弱酸性和过表达的 HO 的特点,通过 Fenton 或类 Fenton 反应催化 HO 转化为强氧化性的˙OH,导致细胞内氧化应激增加,从而促进脂质氧化、蛋白质失活或 DNA 损伤,最终诱导癌细胞凋亡。特别是,CDT 具有肿瘤特异性的优势。然而,CDT 的治疗效果常常取决于 Fenton 反应的催化效率,这需要有足够的 HO 和催化金属离子的存在。相对较低的 HO 浓度和缺乏催化金属离子通常会限制最终的治疗效果。将 CDT 与免疫疗法相结合将是提高治疗效果的有效手段。本文综述了纳米医学在 CDT 与免疫疗法联合应用方面的最新进展。讨论了以肿瘤细胞免疫原性死亡、免疫检查点抑制剂和干扰素基因刺激物(STING)激活为主要免疫治疗策略与 CDT 相结合的相关内容。最后,探讨了临床转化及未来发展方向所面临的挑战和前景。

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