金属配合物在肿瘤化学免疫治疗中的应用前景  

Application Prospect of Metal Complexes in Chemoimmunotherapy of Tumors

作　　者：孙悦文 金素星 王晓勇[1] 郭子建 Yuewen Sun;Suxing Jin;Xiaoyong Wang;Zijian Guo(State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing 210023,China;State Key Laboratory of Coordination Chemistry,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China)

机构地区：[1]南京大学生命科学学院医药生物技术国家重点实验室,南京210023 [2]南京大学化学化工学院配位化学国家重点实验室,南京210023

出　　处：《化学进展》2018年第10期1573-1583,共11页Progress in Chemistry

基　　金：国家自然科学基金项目(No.31570809)资助~~

摘　　要：肿瘤化学免疫治疗是免疫疗法与化学疗法相结合通过协同作用治疗肿瘤的一种新方法。以铂类药物为代表的金属药物是一类重要的化学抗肿瘤药物,其作用机理是与肿瘤细胞DNA形成交联物并阻止其复制;但是,这类药物存在严重的毒性和耐药性问题。近年来发现有些金属配合物在产生细胞毒性的同时,也通过多种机制参与机体的免疫调节过程,其中以诱导免疫原性细胞死亡(ICD)最为常见。本文简要介绍了肿瘤化学免疫治疗的基本概念以及与免疫抑制有关的肿瘤微环境,概述了金属配合物的免疫活性和调节免疫过程的基本原理,并以铂类药物为例总结了金属配合物调节免疫过程的可能途径,最后列举了若干具有ICD诱导潜力和其他免疫调节功能的非铂类金属配合物,指出了目前化学免疫治疗存在的问题和未来的应用潜力。化学治疗与免疫治疗结合既可以利用机体免疫系统增强金属配合物的抗肿瘤效果,又可以减少药物剂量,降低毒副作用,是设计金属抗肿瘤药物的新方向之一。Tumor chemoimmunotherapy is a new method for the treatment of tumors through the combination of immunotherapy and chemotherapy taking advantage of synergistic effect. Metal drugs, represented by platinum agents, are important chemotherapeutic antitumor drugs with cross-linking DNA and preventing DNA replication as the mechanism of action. Nevertheless, these drugs have severe general toxicity and drug resistance. In recent years it was found that in addition to producing cytotoxicity, some metal complexes are involved in the immunomodulation by various mechanisms, including the most common induction of immunogenic cell death （ICD）. This review introduces the basic concepts of tumor chemoimmunotherapy and the tumor microenvironment related to immunosuppression, outlines the immune activities and basic principles for immunomodulation of metal complexes like those of platinum. Finally, some non-platinum metal complexes with ICD-inducing potentials and other immunomodulating functions are described, and the existing problems and application potential of chemoimmunotherapy in the future are indicated. The combination of chemotherapy and immunotherapy not only makes use of the human immune system to enhance the antitumor effect of metal complexes, but also reduces the dose and toxic side effects of drugs, and therefore is one of the new directions for the design of metal-based antitumor drugs.

关 键 词：金属配合物 铂类抗肿瘤药物 化学免疫治疗 无机药物化学 化学生物学 

分 类 号：Q507[生物学—生物化学] O614[理学—无机化学]