文献类型：期刊文献

英文题名：Synergistic effect of the anti-PD-1 antibody with blood stable and reduction sensitive curcumin micelles on colon cancer

作者：Gong, Feirong[1];Ma, Jian-Chao[2,3];Jia, Jianguo[4];Li, Fa-Zhan[2];Wu, Jiao-Lan[2];Wang, Shanfeng[5];Teng, Xin[1];Cui, Zhong-Kai[2,3]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[2]Southern Med Univ, Sch Basic Med Sci, Dept Cell Biol, Guangzhou 510515, Peoples R China;[3]Southern Med Univ, Affiliated Hosp 3, Guangdong Prov Key Lab Bone & Joint Degenerat Dis, Guangzhou, Peoples R China;[4]Fudan Univ, Shanghai Inst Cardiovasc Dis, Zhongshan Hosp, Dept Cardiol, Shanghai, Peoples R China;[5]Sun Yat sen Univ, Sch Mat Sci & Engn, Guangzhou 510275, Peoples R China

年份：2021

卷号：28

期号：1

起止页码：930

外文期刊名：DRUG DELIVERY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000649559900001)】；

基金：This work was supported by the grants from the National Natural Science Foundation of China (Grant Nos. 32070774, 31800840), the Science and Technology Program of Guangzhou (202002030486), and the Key Research & Development Program of Bioland Laboratory (2018GZR110104002).

语种：英文

外文关键词：Telodendrimer micelles; glutathione-triggered release; bioavailability; synergistic effect; cancer immunotherapy

摘要：Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a potent anticancer drug with versatile biological activities, while the clinical translation of curcumin is severely limited due to its hydrophobicity, rapid elimination, and metabolism in the blood circulation. Herein, we aim to unravel the potential of curcumin as a synergistic agent with immunotherapy in the treatment of cancers. In an effort to minimize premature release and improve the systemic bioavailability, a superior blood stable and reduction sensitive curcumin micellar formulation, of which the release can be triggered by cancer cells, is rationally designed. We have synthesized a telodendrimer (mPEG-PLA-(LA)(4)) capable of forming reversible disulfide crosslinked micelles (DCMs). The curcumin loaded DCMs (Cur/DCMs) are spherical with a uniform size of 24.6 nm. The in vitro release profile demonstrates that curcumin releases significantly slower from DCMs than that from non-crosslinked micelles (NCMs), while the release can be accelerated with the increasing concentration of reducing agent glutathione (GSH). Intravenous administration of Cur/DCMs stably retains curcumin in the bloodstream and efficiently improves the systemic bioavailability. Furthermore, Cur/DCMs exhibit synergistic anticancer efficacy when combined with the anti-PD-1 antibody in an MC-38 colon cancer xenograft model. Our results potentiate the integration of blood stable curcumin nanoformulation and immunotherapy for cancer treatment.