Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

作     者：Xiangye Yin Yingjie Zhuang Haiqin Song Yujian Xu Fan Zhang Jianxin Cui Lei Zhao Yingjie Yu Qixu Zhang Jun Ye Youbai Chen Yan Han Xiangye Yin;Yingjie Zhuang;Haiqin Song;Yujian Xu;Fan Zhang;Jianxin Cui;Lei Zhao;Yingjie Yu;Qixu Zhang;Jun Ye;Youbai Chen;Yan Han

作者机构：Department of Plastic and Reconstructive SurgeryThe First Medical CenterChinese PLA General HospitalBeijing100853China Department of General SurgeryRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200023China State Key Laboratory of Organic-Inorganic CompositesBeijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing100029China Department of Plastic SurgeryUniversity of Texas MD Anderson Cancer CenterHoustonTX77030USA State Key Laboratory of Bioactive Substance and Function of Natural MedicinesInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2024年第14卷第3期

页      面：389-400页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the National Natural Science Foundation of China(Grant No.:51803120) 

主　　题：Antibody drug conjugate Cutaneous squamous cell carcinoma DNA damage Platinum drug Targeted therapy 

摘      要：Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology ***(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single ***(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major *** this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and *** so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in ***,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and ***,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.