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新型抗癌治疗药物的细胞内运输:抗体药物偶联物

Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

作者信息

Kalim Muhammad, Chen Jie, Wang Shenghao, Lin Caiyao, Ullah Saif, Liang Keying, Ding Qian, Chen Shuqing, Zhan Jinbiao

机构信息

Department of Biochemistry and Genetics, School of Medicine.

Department of Pharmaceutical Analysis, College of Pharmaceutical Science, Zhejiang University, Hangzhou, People's Republic of China.

出版信息

Drug Des Devel Ther. 2017 Aug 2;11:2265-2276. doi: 10.2147/DDDT.S135571. eCollection 2017.

Abstract

Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

摘要

抗体药物偶联物(ADC)是靶向癌症治疗的一个里程碑,它由与细胞毒性药物化学连接的单克隆抗体组成。ADC的内化通过网格蛋白介导的内吞作用、小窝介导的内吞作用和胞饮作用发生。偶联策略、内吞作用和细胞内运输优化、连接子以及药物化学给研究人员成功根除肿瘤细胞带来了巨大挑战。内吞作用和细胞内运输的这种创造性最近为开发治疗癌细胞的特异性抗体和ADC提供了相当大的动力。有效地强调内吞作用和细胞内运输途径,并设计有效的工程化偶联物和生物实体以极大地促进癌症治疗的高效疗法,具有显著优势。当前的研究阐述了ADC的内吞作用和细胞内运输、蛋白质以及连接子在卸载方面的策略,并且还简要评估了实际适用的ADC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6da/5546728/92615b6b5ebe/dddt-11-2265Fig1.jpg

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