文献类型：期刊文献

英文题名：Self-Delivery Nanoparticles of Amphiphilic Acyclic Enediynes for Efficient Tumor Cell Suppression

作者：Li, Jing[1];Wu, Yuequn[2];Sun, Lili[2];Huang, Shuai[1];Li, Baojun[1];Ding, Yun[1];Hu, Aiguo[1]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai Key Lab Adv Polymer Mat, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2019

卷号：37

期号：5

起止页码：479

外文期刊名：CHINESE JOURNAL OF CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000466442600008)】；

基金：The financial supports from the National Natural Science Foundation of China (Nos. 21871080, 21503078, 21474027), the Fundamental Research Funds for the Central Universities (No. 22221818014), and the Shanghai Leading Academic Discipline Project (B502) are greatly acknowledged. AH thanks the "Eastern Scholar Professorship" support from Shanghai Local Government. AH thanks Prof. Runhui Liu for his kindly advice in cell experiments.

语种：英文

外文关键词：radicals; DNA cleavage; amphiphiles; antibiotics; cyclization; self-assembly

摘要：main observation and conclusion Four acyclic maleimide-based enediyne compounds with different hydrophilicity were synthesized through Sonogashira reaction to reveal a self-delivery antitumor drug platform. As proved by ESR analysis, the enediyne compounds undergo Bergman-like cyclization and generate diradical intermediates at physiological temperature, which are able to induce DNA-cleavage through the abstraction of H atoms from the sugar-phosphate backbones. When the critical aggregation concentration is reached in water, the amphiphilic enediyne compounds self-assemble into nanoparticles and possess the self-delivery ability to be facilely admitted by tumor cells, resulting in greatly improved cytotoxicity (IC50 down to 10 mu mol center dot L-1) and much higher tumor cell apoptosis rate (up to 86.6%) in comparison with either the hydrophilic or the lipophilic enediyne compound. The enhanced endocytosis of the amphiphilic enediyne compounds was further confirmed through confocal laser scanning microscopy analysis. The unveiled relationship between the hydrophilicity of enediyne drugs and their therapeutic efficacy will provide a guideline for the design of new self-delivery drugs employed in medicinal applications.