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

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

扫码查看
原文链接
  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
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 therapy.Cetuximab(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 use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(Ⅳ)prodrug(C8Pt(Ⅳ))and Cet.The so-called antibody-platinum(Ⅳ)prodrugs conjugates,named Cet-C8Pt(Ⅳ),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(Ⅳ)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,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.

Antibody drug conjugateCutaneous squamous cell carcinomaDNA damagePlatinum drugTargeted therapy

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

展开 >

Department of Plastic and Reconstructive Surgery,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China

Department of General Surgery,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200023,China

State Key Laboratory of Organic-Inorganic Composites,Beijing Laboratory of Biomedical Materials,Beijing University of Chemical Technology Beijing,100029,China

Department of Plastic Surgery,University of Texas,MD Anderson Cancer Center,Houston,TX 77030,USA

State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050,China

展开 >

2024

10.1016/j.jpha.2023.11.002

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(3)