文献类型：期刊文献

英文题名：Self-delivery nanoparticles of an amphiphilic irinotecan-enediyne conjugate for cancer combination chemotherapy

作者：Li, Jing[1];Li, Baojun[1];Sun, Lili[2];Duan, Bing[2];Huang, Shuai[1];Yuan, Yuan[2];Ding, Yun[1];Hu, Aiguo[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, Sch Mat Sci & Engn, 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：7

期号：1

起止页码：103

外文期刊名：JOURNAL OF MATERIALS CHEMISTRY B

收录：;EI(收录号：20185206286467);WOS:【SCI-EXPANDED(收录号:WOS:000454835500007)】；

基金：The financial support from the National Natural Science Foundation of China (21474027, 21503078, 21871080), the Fundamental Research Funds for the Central Universities (22221818014), and Shanghai Leading Academic Discipline Project (B502) is greatly acknowledged. AH thanks the "Eastern Scholar Professorship" support from Shanghai Local Government. JL thanks Mr Yuequn Wu and Prof. Runhui Liu for their kindly help in cell experiments.

语种：英文

外文关键词：Molecular biology - Controlled drug delivery - Magnetic moments - Self assembly - Chemotherapy - Tumors - Cell death - Targeted drug delivery

摘要：An amphiphilic small molecular drug self-delivery system was designed by linking a hydrophilic topoisomerase I inhibitor irinotecan (Ir) with a lipophilic cytotoxic enediyne (EDY) antibiotic through an ester bond. The maleimide-based EDY with a pendant carboxyl group was synthesized in four steps from commercially available reagents. The EDY compound possesses the ability to generate radical intermediates at physiological temperature as demonstrated by electron spin resonance analysis and further causes DNA-cleavage and tumor cell suppression. The self-delivery system prepared by the combination of two anticancer drugs, EDY and Ir, formed nanoparticles' self-assembly with a size of around 60 nm in aqueous solution, enabling the drugs to accumulate in tumor tissues through the enhanced permeability and retention effect. With high drug loading capacity (100%), the Ir-EDY nanoparticles entered tumor cells through endocytosis and possessed strong synergistic effects, inducing tumor cell death through the cell apoptosis pathway efficiently.