Amphiphilic drug-drug conjugate for cancer therapy with combination of chemotherapeutic and antiangiogenesis drugs  

作　　者：Mo Sun Qiuhui Qian Leilei Shi Li Xu Qunfang Liu Linzhu Zhou Xinyuan Zhu Jian-Min Yue Deyue Yan 

机构地区：[1]School of Chemistry and Chemical Engineering,State Key Laboratory of Metal Matrix Composites,Shanghai Jiao Tong University,Shanghai 200240,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Science China Chemistry》2020年第1期35-41,共7页中国科学（化学英文版）

基　　金：supported by the National Basic Research Program(2015CB931801);the National Natural Science Foundation of China(51690151,21504055)

摘　　要：The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels.However,using angiogenesis inhibitors alone does not meet the cancer treatment needs.Herein,we used the amphiphilic drug-drug conjugate(ADDC)strategy to fabricate a new drug conjugate with the combination of chemotherapeutic drug and antiangiogenesis drug together.With one-step esterification of hydrophilic floxuridine(FUDR)and hydrophobic pseudolaric acid B(PAB),the conjugate was synthesized.The amphiphilic property of FUDR-PAB conjugate induced the self-assembly to form nanoparticles in water.From further in vitro and in vivo experiments,this FUDR-PAB conjugate does not only have a high antitumor effect,but also shows efficient antianiogenesis property.These results offer a promising ADDC strategy for designing drugs with combination of chemotherapeutic drug and antiangiogenesis drug together.The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels. However, using angiogenesis inhibitors alone does not meet the cancer treatment needs. Herein, we used the amphiphilic drug-drug conjugate(ADDC) strategy to fabricate a new drug conjugate with the combination of chemotherapeutic drug and antiangiogenesis drug together. With one-step esterification of hydrophilic floxuridine(FUDR) and hydrophobic pseudolaric acid B(PAB), the conjugate was synthesized. The amphiphilic property of FUDR-PAB conjugate induced the self-assembly to form nanoparticles in water. From further in vitro and in vivo experiments, this FUDR-PAB conjugate does not only have a high antitumor effect, but also shows efficient antianiogenesis property. These results offer a promising ADDC strategy for designing drugs with combination of chemotherapeutic drug and antiangiogenesis drug together.

关 键 词：nanoparticle combination therapy cancer treatment supramolecular chemistry 

分 类 号：R730.5[医药卫生—肿瘤]