文献类型：期刊文献

英文题名：Safe and Efficacious Diphtheria Toxin-Based Treatment for Melanoma: Combination of a Light-On Gene-Expression System and Nanotechnology

作者：Xu, Jiajun[1];He, Muye[1];Hou, Xinyu[1];Wang, Yan[1];Shou, Chenting[1];Cai, Xiaoran[1];Yuan, Zeting[1,8];Yin, Yu[1];Lan, Minbo[2];Lou, Kaiyan[1,4,5];Zhao, Yuzheng[3,6,7];Yang, Yi[3,6,7];Chen, Xianjun[3,6,7];Gao, Feng[1,2,3,9]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Dept Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[6]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg Technol, State Key Lab Bioreactor Engn, Synthet Biol & Biotechnol Lab, Shanghai 200237, Peoples R China;[7]East China Univ Sci & Technol, CAS Ctr Excellence Brain Sci, Optogenet & Mol Imaging Interdisciplinary Res Ctr, Shanghai 200237, Peoples R China;[8]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[9]East China Univ Sci & Technol, Sch Pharm, Minist Educ, Engn Res Ctr Pharmaceut Proc Chem, Shanghai 200237, Peoples R China

年份：2020

卷号：17

期号：1

起止页码：301

外文期刊名：MOLECULAR PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000506713600028)】；

基金：This work was supported by Shanghai Municipal Natural Science Foundation (contract No. 17ZR1406600), National Natural Science Foundation of China (grant No. 81973700), Science and Technology Commission of Shanghai Municipality (contract No. 10DZ2220500), and The Shanghai Committee of Science and Technology (grant No. 11DZ2260600).

语种：英文

外文关键词：Light-On gene-expression system; nanotechnology; diphtheria toxin; antitumor; melanoma

摘要：The controversy surrounding the use of diphtheria toxin (DT) as a therapeutic agent against tumor cells arises mainly from its unexpected harmfulness to healthy tissues. We encoded the cytotoxic fragment A of DT (DTA) as an objective gene in the LightOn gene-expression system to construct plasmids pGAVPO (pG) and pU5-DTA (pDTA). Meanwhile, a cRGD-modified ternary complex comprising plasmids, chitosan, and liposome (pG&pDTA@cRGD-CL) was prepared as a nanocarrier to ensure transfection efficiency. Benefiting from spatiotemporal control of this light-switchable transgene system and the superior tumor targeting of the carrier, toxins were designed to be expressed selectively in illuminated lesions. In vitro studies suggested that pG&pDTA@cRGD-CL exerted arrest of the S phase in B16F10 cells upon blue light irradiation and, ultimately, induced the apoptosis and necrosis of tumor cells. Such DTA-based treatment exerted enhanced antitumor activity in mice bearing B16F10 xenografts and displayed prolonged survival time with minimal side effects. Hence, we described novel DTA-based therapy combined with nanotechnology and the Light-On gene-expression system: such treatment could be a promising strategy against melanoma.