蛋白降解靶向纳米嵌合体在肿瘤治疗中的应用进展  

Advances of nano-proteolysis-targeting chimeras in cancer therapy

作　　者：李永正 张静娟 宋健 祁迎秋 Li Yongzheng;Zhang Jingjuan;Song Jian;Qi Yingqiu(Department of Pharmacology,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450001,Henan,China;Department of Burns and Plastic Surgery,The Second Hospital of Shandong University,Jinan 250033,Shandong,China)

机构地区：[1]郑州大学基础医学院药理学系,河南郑州450001 [2]山东大学第二医院烧伤整形科,山东济南250033

出　　处：《中国医学前沿杂志（电子版）》2024年第10期26-34,I0002,共10页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：国家自然科学基金面上项目(32371524)。

摘　　要：蛋白降解靶向嵌合体(proteolysis-targeting chimeras,PROTACs)技术是一种新兴的治疗手段,通过特异性降解肿瘤相关蛋白,实现了对癌细胞的精准打击,而不影响正常细胞,为癌症治疗提供了新路径。然而,PROTACs分子在实际应用中仍面临诸多挑战,如溶解度低、器官靶向性差,脱靶效应以及代谢不稳定等。蛋白降解靶向纳米嵌合体(nano-proteolysis-targeting chimeras,nano-PROTACs)是纳米技术与PROTAC技术相结合的产物,为克服当前癌症治疗中的种种挑战提供了新的解决思路。我们结合最新的研究进展,总结了用于肿瘤治疗的nano-PROTACs的种类,并概述了不同种类nano-PROTACs的设计策略,包括递送系统、装载方法、释放方式以及联合治疗效果等。进一步加深对这一快速发展的领域的理解,以期为基于PROTAC技术的抗肿瘤药物研发提供有益的思路和参考。Proteolysis-targeting chimera(PROTAC)technology,as an emerging therapeutic approach,achieves precise targeting of cancer cells by specifically degrading tumor-associated proteins without affecting normal cells,offering a novel pathway for cancer treatment.However,PROTACs still have numerous challenges and limitations in practical applications,such as suboptimal water solubility,lack of tumor-targeting,off-target effects and metabolic instability.Nano-proteolysis-targeting chimeras(Nano-PROTACs),a product of the fusion between nanotechnology and PROTAC technology,presents a powerful strategy for overcoming various challenges in current cancer therapy.In this review,we summarize the types of Nano-PROTACs used in tumor therapy based on the latest research progress.Furthermore,we outline the design strategies for different Nano-PROTACs,encompassing delivery systems,methods of loading and releasing mechanisms and combinatorial therapeutic effects.Our summary in this review aims to shed light on future Nano-PROTACs design and promote the degradation technologies for anti-tumor based on the PROTAC mechanism.

关 键 词：蛋白降解靶向嵌合体 纳米技术 蛋白降解靶向纳米嵌合体 肿瘤治疗 

分 类 号：R730.5[医药卫生—肿瘤]