Kinetically-stable small-molecule prodrug nanoassemblies for cancer chemotherapy

作者全名："Zheng, Yaxin; Ying, Xue; Su, Yue; Jin, Xuan; Xu, Qiulin; Li, Yang"

作者地址："[Li, Yang] Chongqing Med Univ, Coll Pharm, Dept Pharmaceut, Chongqing 400016, Peoples R China; [Zheng, Yaxin; Ying, Xue; Su, Yue; Jin, Xuan; Xu, Qiulin] Chengdu Med Coll, Sch Pharm, Key Lab Sichuan Prov Specif Struct Small Mol Drug, Chengdu, Peoples R China"

通信作者："Li, Y (corresponding author), Chongqing Med Univ, Coll Pharm, Dept Pharmaceut, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF PHARMACEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000628677400066

JCR分区：Q1

影响因子：5.8

年份：2021

卷号：597

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Kinetic stability; Self-delivering; Lipid-drug conjugate; Camptothecin; Self-assemble; Cancer Chemotherapy

摘要："Self-delivering nanocarrier based on the small-molecule prodrug nanoassemblies (NAs) have been widely used for the efficient delivery of chemotherapeutics, but the effect of kinetic stability of NAs on their delivery performance has not been illuminated. In this study, two camptothecin (CPT)-oleic acid (OA) prodrugs were used to fabricate self-assembling nanorods with similar size distribution, zeta potential and morphology but having sharply different kinetic stability, which provided an ideal platform to investigate the effects of kinetic stability. It is found that the nanorods with high kinetic stability showed a lower in vitro cytotoxicity, but were more effective to inhibit the tumor growth probably by decreasing the premature CPT release and subsequent generation of the inactive carboxylate CPT. However, such kinetically stable nanomds also resulted in the increased toxicity, probably due to the high prodrug accumulation in tissues after multiple injections. These results outlined the pivotal role of kinetic stability in determining antitumor efficacy of prodrug NAs, which provided a new insight into the delivery mechanism for the small-molecule prodrug self-delivering nanosystems."

基金机构：National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81760421]; Foundation of Chengdu Medical College [CYZ1917]; Foundation of Collaborative Innovation Center of Sichuan for Elderly Care and Health [20Z022]; Foundation of Development and Regeneration Key Laboratory of Sichuan Province [SYS17-009]; Foundation for New Teacher Training Program of Chongqing Medical University [YXY2020XSZ02]

基金资助正文："This research was supported by National Science Foundation of China (81760421), Foundation of Chengdu Medical College (CYZ1917), Foundation of Collaborative Innovation Center of Sichuan for Elderly Care and Health (20Z022), Foundation of Development and Regeneration Key Laboratory of Sichuan Province (SYS17-009) and Foundation for New Teacher Training Program of Chongqing Medical University (YXY2020XSZ02)."