文献类型：期刊文献

英文题名：Peptide-Mimicking Poly(2-oxazoline)s Possessing Potent Antifungal Activity and BBB Penetrating Property to Treat Invasive Infections and Meningitis

作者：Jiang, Weinan[1,2,3];Zhou, Min[2];Chen, Sheng[2];Xie, Jiayang[2];Chen, Minzhang[2];Zhang, Haodong[2];Wu, Yueming[2];Chen, Xin[3];Liu, Runhui[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Frontiers Sci Ctr Materiobiol & Dynam Chem, Res Ctr Biomed Mat,Minist Educ,Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2023

卷号：145

期号：47

起止页码：25753

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20234915173805);WOS:【SCI-EXPANDED(收录号:WOS:001111118300001)】；

基金：The authors also thank the Research Center of Analysis and Test of East China University of Science and Technology for the help with the characterization. The authors acknowledge the support of the Analysis and Testing Center of School of Chemical Engineering, East China university of Science and Technology. The authors thank the staff members of the Integrated Laser Microscopy System at the National Facility for Protein Science in Shanghai (NFPS), Zhangjiang Lab, China, for providing technical support and assistance in data collection and analysis. The authors thank Dr. Bingyang Shi, Dr. Meng Zheng, and Dr. Dongya Zhang from Henan University for the generous help with the in vitro transwell study.

语种：英文

外文关键词：Antifungal agents - Drug interactions - Mammals - Peptides

摘要：Invasive fungal infections, including meningitis, cause a high mortality rate due to few available antifungal drugs and frequently associated side effects and quick emergence of drug-resistant fungi. The restrictive permeability of the blood-brain barrier (BBB) further limits the efficacy of antifungal agents substantially in treating meningitis. Hereby, we design and synthesize guanidinium-functionalized poly-(2-oxazoline)-s by mimicking cell-penetrating peptides. The optimal polymer, PGMeOx(10) bearing a methylene spacer arm, displays potent activities against the drug-resistant fungi and biofilm, negligible toxicity, and insusceptibility to antimicrobial resistance. Moreover, PGMeOx(10) can break BBB retractions to exert promising antifungal functions in the brain. PGMeOx(10) demonstrates potent in vivo antifungal therapeutic efficacy in mouse models including skin infection, systemic infections, and meningitis. PGMeOx(10) effectively rescues infected mice and reduces fungal burden and inflammation in the brain. These results and the excellent biosafety of poly-(2-oxazoline)-s indicate the effectiveness and potential of our strategy to design promising antifungal agents in treating systemic infections and meningitis.