文献类型：期刊文献

英文题名：Construction of a pH-responsive, ultralow-dose triptolide nanomedicine for safe rheumatoid arthritis therapy

作者：Liu, Yang[1,3,4];Jin, Jianqiu[1,2];Xu, Hao[1,3,4];Wang, Chao[1,2];Yang, Yanping[1,3,4];Zhao, Yongjian[1,3,4];Han, Haihui[1,3,4];Hou, Tong[1,3,4];Yang, Guoliang[1,2];Zhang, Li[1,3,4];Wang, Yongjun[1,3,4];Zhang, Weian[2];Liang, Qianqian[1,3,4]

机构：[1]Shanghai Univ Tradit Chinese Med, Longhua Hosp, 725 South Wanping Rd, Shanghai 200032, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Spine Inst, 725 South Wanping Rd, Shanghai 200032, Peoples R China;[4]Shanghai Univ Tradit Chinese Med, Key Lab Theory & Therapy Muscles & Bones, Minist Educ, 1200 Cailun Rd, Shanghai 201203, Peoples R China

年份：2021

卷号：121

起止页码：541

外文期刊名：ACTA BIOMATERIALIA

收录：;EI(收录号：20215111336349);WOS:【SCI-EXPANDED(收录号:WOS:000614494800006)】；

基金：This work was supported by research grants from National key research and development project (2018YFC1704300) to YJW, National Natural Science Foundation (81822050 and 81920108032 to LQQ, 81930116 to YJW), Leading medical talents in Shanghai (2019LJ02 to QQL), Dawn plan of Shanghai Municipal Education Commission (19SG39 to QQL), The program for innovative research team of ministry of science and technology of China (2015RA4002 to YJW), "Innovation Team" development projects (IRT1270 to YJW), Shanghai TCM Medical Center of Chronic Disease (2017ZZ01010 to YJW), Three year action plan of Shanghai to further speed up the development of traditional Chinese Medicine (ZY(2018-2020)-CCCX-3003 to YJW).

语种：英文

外文关键词：Rheumatoid arthritis; Triptolide; POSS-PCL-b-PDMAEMA

摘要：Rheumatoid arthritis (RA) is a chronicautoimmune disease, marked by joint swelling and pain, articular synovial hyperplasia, as well as cartilage and bone destruction. Triptolide (TP) is an anti-inflammatory molecule but its use to treat RA is limited due to poor solubility and extremely high toxicity. In this study, by encapsulating TP into a star-shaped amphiphilic block copolymer, POSS-PCL-b-PDMAEMA, we engineered a pH-sensitive TP-loaded nanomedicine (TP@NPs) to simultaneously reduce the toxicity of TP and improve its therapeutic efficacy. TP@NPs shows a uniform spherical structure with a hydrodynamic diameter of similar to 92 nm and notable pH-responsiveness. In vitro TP@NPs showed reduced cytotoxicity and cell apoptosis of treated RAW264.7 cells compared to free TP. And in vivo intravenous injection of indocyanine green-labeled NPs into a collagen-induced arthritis model in mice showed that the engineered compound had potent pharmacokinetic and pharmacodynamic profiles, while exhibiting significant cartilage protective and anti-inflammatory effects with a better efficacy and neglible systemic toxicity even at an ultralow dose compared to free TP. These results suggest that TP@NPs may be a safe and effective therapy for RA and other autoimmune diseases. Statement of Significance This work provides a new strategy for delivery of ultraow-dose Triptolide (TP) using acidic microenvironment responsive micelles for effective treatment of rheumatoid arthritis (RA).This is the first report on fabricating an inflammatory acidic microenvironment responsive TP-loaded nanomedicine with ultralow drug dosage for safe and effective RA therapy. The responsive drug release could widen the therapeutic window of the compound and thus mitigate any toxicity. (c) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.