Citation: Penghui Chen, Jianmian Fu, Shule Hou, Jifang Zhang, Tianyu Gong, Jingyi Zhu, Sihan Huang, Yuxuan Wu, Qing Zhang, Maoli Duan, Jiarui Chen, Jin Xie, Yangyang Yang, Jun Yang, Xuhong Qian. A coacervate-based redox-responsive cytoplasmic delivery system for antioxidant macromolecule to rescue sensorineural hearing loss[J]. Chinese Chemical Letters, ;2026, 37(6): 111447. doi: 10.1016/j.cclet.2025.111447 shu

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

Penghui Chen ^{a, d, e, 1} ,
Jianmian Fu ^{b, 1} ,
Shule Hou ^{a, d, e, 1} ,
Jifang Zhang ^{a, d, e} ,
Tianyu Gong ^{a, d, e} ,
Jingyi Zhu ^{a, d, e} ,
Sihan Huang ^{a, d, e} ,
Yuxuan Wu ^{a, d, e} ,
Qing Zhang ^{a, d, e} ,
Maoli Duan ^{g, h} ,
Jiarui Chen ^{f, *,} ,
Jin Xie ^{a, d, e, *,} ,
Yangyang Yang ^{b, *,} ,
Jun Yang ^{a, d, e, *,} ,
Xuhong Qian ^{b, c}

a.
Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200082, China
b.
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
c.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
d.
Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200082, China
e.
Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200082, China
f.
Department of Otolaryngology-Head and Neck Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
g.
Ear Nose and Throat Patient Area, Trauma and Reparative Medicine Theme, Karolinska University Hospital, Stockholm 17717, Sweden
h.
Division of Ear, Nose and Throat Diseases, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm 17717, Sweden

drchenjiarui@163.com

xjmdsh@163.com

triyang@ecust.edu.cn

yangjun@xinhuamed.com.cn

Received Date: 22 March 2025
Revised Date: 9 June 2025
Accepted Date: 10 June 2025
Available Online: 11 June 2025

Figures(4)

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.
- Coacervate microdroplets,
- Redox-responsive release,
- Targeted intracellular delivery,
- Sensorineural hearing loss,
- Antioxidant therapy
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