American Association for Cancer Research
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Figure S5-S6 from New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

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journal contribution
posted on 2023-03-31, 01:10 authored by Hangxiang Wang, Zhongjie Lu, Lijiang Wang, Tingting Guo, Jiaping Wu, Jianqin Wan, Liqian Zhou, Hui Li, Zhen Li, Donghai Jiang, Penghong Song, Haiyang Xie, Lin Zhou, Xiao Xu, Shusen Zheng

In vivo drug plasma concentration-time profile and drug tissue biodistribution


National Natural Science Foundation of China

Natural Science Foundation of Zhejiang Province



The therapeutic index for chemotherapeutic drugs is determined in part by systemic toxicity, so strategies for dose intensification to improve efficacy must also address tolerability. In addressing this issue, we have investigated a novel combinatorial strategy of reconstructing a drug molecule and using sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines (SNM). Using cabazitaxel as a target agent, we established that individual synthetic prodrugs tethered with polyunsaturated fatty acids were capable of recapitulating self-assembly behavior independent of exogenous excipients. The resulting SNM could be further refined by PEGylation with amphiphilic copolymers suitable for preclinical studies. Among these cabazitaxel derivatives, docosahexaenoic acid–derived compound 1 retained high antiproliferative activity. SNM assembled with compound 1 displayed an unexpected enhancement of tolerability in animals along with effective therapeutic efficacy in a mouse xenograft model of human cancer, compared with free drug administered in its clinical formulation. Overall, our studies showed how attaching flexible lipid chains to a hydrophobic and highly toxic anticancer drug can convert it to a systemic self-deliverable nanotherapy, preserving its pharmacologic efficacy while improving its safety profile. Cancer Res; 77(24); 6963–74. ©2017 AACR.

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