文献类型：期刊文献

英文题名：Effective combinatorial antifungal therapy using a host defense peptide mimic that self-assembles into delivery micelles

作者：Liu, Longqiang[1];Zhou, Min[1];Xiao, Ximian[2];Cong, Zihao[2,3];Wu, Yueming[3];Xie, Jiayang[2];Zhang, Qiang[3,4];Zhang, Junyu[2,3];Jiang, Weinan[2];Liu, Runhui[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Chinese Acad Sci, Suzhou Inst Biomed Engn & Technol, Suzhou, Peoples R China;[3]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Mat Sci & Engn,Shanghai Frontiers Sci Ctr Opto, Engn Res Ctr Biomed Mat,Minist Educ,Key Lab Ultraf, Shanghai, Peoples R China;[4]Shanghai Jiao Tong Univ, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China

年份：2026

外文期刊名：NATURE BIOTECHNOLOGY

收录：;EI(收录号：20260119857897);WOS:【SCI-EXPANDED(收录号:WOS:001652370200001)】；

基金：This research was supported by the Chinese Academy of Sciences Project for Young Scientists in Basic Research (YSBR-111, to R.L.), the National Natural Science Foundation of China (T2325010, to R.L.; 22475069 and 52203162, to Y.W.; 22305082, to M.Z.), the National Key Research and Development Program of China (2022YFC2303100, to R.L.), the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) and the Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry (Changchun Institute of Applied Chemistry, Chinese Academy of Sciences). We thank Research Center of Analysis and Test of East China University of Science and Technology and the Analysis and Testing Center of School of Chemical Engineering at East China University of Science and Technology for support with the characterization. We thank the staff members of the Integrated Laser Microscopy System at the National Facility for Protein Science in Shanghai, Zhangjiang Lab for providing technical support and assistance in data collection and analysis.

语种：英文

外文关键词：Antifungal agents - Controlled drug delivery - Diseases - Fungi - Fungicides - Peptides - Targeted drug delivery

摘要：The synergistic combination of two antimicrobial drugs is a promising therapeutic modality for many infectious diseases. However, systemic fungal infections still have a high mortality rate because of distinct in vivo distributions of the two drugs. Here we address this challenge by designing an antifungal polymer that forms micelles suitable for delivering a second antifungal agent to achieve temporal and spatial consistency of delivery. We show that the polymer, which mimics host defense peptides, exerts a synergistic effect with the antifungal amphotericin B (AmB). The AmB-encapsulated micelles (AmBmicelles) greatly reduce the toxicity of AmB through slow release and expand its therapeutic window in vivo. AmBmicelles can selectively target fungal pathogens through charge interactions with the fungal membrane. In mouse models of systemic candidiasis and cryptococcal meningitis, AmBmicelles increase the survival rate by 67-100% compared to the state-of-the-art drug AmBisome or AmBisome and 5-flucytosine combination, suggesting that the strategy may be effective in combating drug-resistant fungal infections including meningitis.