ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss

Zeqi Zhao; Zhengzhong Han; Konduru Naveena; Guanxiong Lei; Shiwei Qiu; Xuanyi Li; Ting Li; Xi Shi; Wei Zhuang; Yalan Li; Yuehua Qiao; Hongmei Liu

doi:10.1021/acsami.0c21151

ROS-Responsive Nanoparticle as a Berberine Carrier for OHC-Targeted Therapy of Noise-Induced Hearing Loss

ACS Appl Mater Interfaces. 2021 Feb 17;13(6):7102-7114. doi: 10.1021/acsami.0c21151. Epub 2021 Feb 2.

Authors

Zeqi Zhao^{1

2

3}, Zhengzhong Han⁴, Konduru Naveena¹, Guanxiong Lei^{5

6}, Shiwei Qiu¹, Xuanyi Li², Ting Li¹, Xi Shi¹, Wei Zhuang¹, Yalan Li¹, Yuehua Qiao^{1

2

3}, Hongmei Liu^{7

8}

Affiliations

¹ Institute of Audiology and Balance Science, Xuzhou Medical University, Xuzhou 221002, PR China.
² Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China.
³ Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou 221002, PR China.
⁴ Xuzhou Children's Hospital, Xuzhou 221002, PR China.
⁵ Key Laboratory of Medical Imaging and Artifical Intelligence of Hunan Province, Xiangnan University, Chenzhou 423000, PR China.
⁶ Clinical College, Xiangnan University, Chenzhou 423000, PR China.
⁷ Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, PR China.
⁸ Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China.

PMID: 33528239
DOI: 10.1021/acsami.0c21151

Abstract

Overproduction of reactive oxygen species (ROS) and inflammation are two key pathogeneses of noise-induced hearing loss (NIHL), which leads to outer hair cell (OHC) damage and hearing loss. In this work, we successfully developed ROS-responsive nanoparticles as berberine (BBR) carriers (PL-PPS/BBR) for OHC-targeted therapy of NIHL: Prestin-targeting peptide 2 (PrTP2)-modified nanoparticles (PL-PPS/BBR), which effectively accumulated in OHC areas, and poly(propylene sulfide)₁₂₀ (PPS₁₂₀), which scavenged ROS and converted to poly(propylene sulfoxide)₁₂₀ in a ROS environment to disintegrate and provoke the rapid release of BBR with anti-inflammatory and antioxidant effects. In this study, satisfactory anti-inflammatory and antioxidant effects of PL-PPS/BBR were confirmed. Immunofluorescence and scanning electron microscopy (SEM) images showed that PL-PPS/BBR effectively accumulated in OHCs and protected the morphological integrity of OHCs. The auditory brainstem response (ABR) results demonstrated that PL-PPS/BBR significantly improved hearing in NIHL guinea pigs after noise exposure. This work suggested that PL-PPS/BBR may be a new potential treatment for noise-associated injury with clinical application.

Keywords: berberine; drug delivery; noise-induced hearing loss; outer hair cells; radical oxygen species.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antioxidants / chemistry
Antioxidants / pharmacology*
Berberine / chemistry
Berberine / pharmacology*
Disease Models, Animal
Drug Carriers / chemistry
Evoked Potentials, Auditory, Brain Stem / drug effects
Guinea Pigs
Hair Cells, Auditory, Outer / drug effects*
Hearing Loss, Noise-Induced / drug therapy*
Molecular Structure
Nanoparticles / chemistry
Particle Size
Reactive Oxygen Species / chemistry*
Reactive Oxygen Species / metabolism
Surface Properties

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antioxidants
Drug Carriers
Reactive Oxygen Species
Berberine