文献类型：期刊文献

英文题名：A coacervate-based redox-responsive cytoplasmic delivery system for antioxidant macromolecule to rescue sensorineural hearing loss

作者：Chen, Penghui[1,4,5];Fu, Jianmian[2];Hou, Shule[1,4,5];Zhang, Jifang[1,4,5];Gong, Tianyu[1,4,5];Zhu, Jingyi[1,4,5];Huang, Sihan[1,4,5];Wu, Yuxuan[1,4,5];Zhang, Qing[1,4,5];Duan, Maoli[7,8];Chen, Jiarui[6];Xie, Jin[1,4,5];Yang, Yangyang[2];Yang, Jun[1,4,5];Qian, Xuhong[2,3]

机构：[1]Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Shanghai 200082, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[4]Shanghai Jiao Tong Univ, Sch Med, Ear Inst, Shanghai 200082, Peoples R China;[5]Shanghai Key Lab Translat Med Ear & Nose Dis, Shanghai 200082, Peoples R China;[6]Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Sch Med, Dept Otolaryngol & Head & Neck Surg, Shanghai 200127, Peoples R China;[7]Karolinska Univ Hosp, Ear Nose & Throat Patient Area, Trauma & Reparat Med Theme, S-17717 Stockholm, Sweden;[8]Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Ear Nose & Throat Dis, S-17717 Stockholm, Sweden

年份：2026

卷号：37

期号：6

外文期刊名：CHINESE CHEMICAL LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001715281000001)】；

基金：This work is supported by grants from National Key R&D Program of China (Nos. 2024YFC2511100 and 2024YFC2511105 to J. Yang) , National Natural Science Foundation of China (Nos. 82230035 and 82271179 to J. Yang, 82000977 and 82371150 to S. Hou, 820 0 0989 to P. Chen) , and Shanghai Sailing Program (Nos. 20YF1428800 to P. Chen, 20YF1428900 to S. Hou) .

语种：英文

外文关键词：Coacervate microdroplets; Redox-responsive release; Targeted intracellular delivery; Sensorineural hearing loss; Antioxidant therapy

摘要：Sensorineural hearing loss (SNHL) is a prevalent global health issue, primarily caused by excessive generation of reactive oxygen species (ROS) due to acoustic trauma, aging, and ototoxic drugs. Natural antioxidant enzymes, such as catalase (CAT), possess remarkable ROS scavenging capabilities and hold significant potential for SNHL treatment. However, their clinical application is hindered by inefficient delivery and limited stability. Here, we introduce a novel peptide-oligosaccharide conjugate, sELP-ON, which forms coacervate microdroplets via liquid-liquid phase separation. These microdroplets efficiently encapsulate and stably carry CAT, releasing it in a glutathione-triggered, redox-responsive manner. The CAT-loaded sELP-ON (sELP-ON@CAT) enhanced cellular uptake through direct cytoplasmic internalization and demonstrates a more robust ROS scavenging activity than naked CAT treatment. Local administration of sELP-ON@CAT in an acoustic injury mouse model effectively rescues hearing loss by reducing cochlear ROS levels, thereby mitigating hair cell loss, ribbon synapse depletion, stria vascularis shrinkage and spiral ganglion neuron degeneration. In summary, our innovative coacervate microdroplet system enables targeted, redox-responsive cytoplasmic delivery of macromolecular antioxidants, offering a novel and effective strategy for treating SNHL. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.