多肽-药物键合物用于肿瘤靶向诊疗  

Peptide-drug conjugates for tumor targeted diagnosis and treatment

作　　者：陈颖 郑蓉蓉 李仕颖 CHEN Ying;ZHENG Rong-rong;LI Shi-ying(School of Pharmacy,Guangzhou Medical University,Guangzhou 511436,China)

机构地区：[1]广州医科大学药学院,广东广州511436

出　　处：《药学学报》2023年第8期2341-2352,共12页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划项目(2021YFD1800600);广东省自然科学基金项目(2021B1515020043)。

摘　　要：癌症仍是威胁人类生命和健康的主要疾病之一。目前,如何实现肿瘤精准诊疗是癌症治疗的最大挑战。前体药物利用靶向分子的肿瘤特异性将抗癌药物靶向递送至肿瘤部位,能够有效提高药物生物利用度、治疗效果和安全性,是当前抗癌药物的研发热点。前药的靶向分子主要有核酸适体、聚合物、抗体、多肽等,其中多肽具有生物相容性好、降解性能可控、生物体内响应性高和制备方法简单易行等优点,被广泛用来构建多肽-药物键合物(peptide-drug conjugates,PDC)前药,实现对肿瘤的靶向治疗。近年来,随着噬菌体肽库技术和多肽标准固相合成技术的发展,越来越多的靶向多肽被发现和有效合成修饰,为PDC的发展提供了有力支持。本文简要介绍了PDC中功能型多肽和连接子的种类及功能,并详细论述了PDC在化学疗法、免疫疗法和光动力疗法在肿瘤靶向诊疗中的应用,最后总结了PDC药物开发所面临的困难。Cancer is still one of the major diseases threatening human life and health.At present,how to achieve precise diagnosis and treatment of tumors is the biggest challenge in cancer treatment.Prodrugs use the tumor specificity of targeting molecules to deliver anticancer drugs to tumor sites,which can effectively improve drug bioavailability,therapeutic efficacy and safety,and are currently a hot spot in the research and development of anticancer drugs.The targeting molecules of prodrugs mainly include nucleic acid aptamers,polymers,antibodies,polypeptides,etc.Among them,polypeptides have the advantages of good biocompatibility,controllable degradation performance,high in vivo responsiveness,and simple and easy preparation methods,and are widely used.It is used to construct peptide-drug conjugates(PDC)prodrugs to achieve targeted therapy of tumors.In recent years,with the development of phage peptide library technology and peptide standard solid-phase synthesis technology,more and more targeted peptides have been discovered and effectively synthesized and modified,providing strong support for the development of PDC.This review briefly introduces the types and functions of functional peptides and linkers in PDC,and discusses the application of PDC in chemotherapy,immunotherapy and photodynamic therapy in tumor targeted diagnosis and treatment,and finally summarizes the difficulties faced by PDC drug development.

关 键 词：多肽 连接子 抗肿瘤药物 肿瘤靶向 药物递送系统 

分 类 号：R945[医药卫生—微生物与生化药学]