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ROS 响应性纳米颗粒作为盐酸小檗碱载体用于噪声性听力损失的毛细胞靶向治疗。

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

机构信息

Institute of Audiology and Balance Science, Xuzhou Medical University, Xuzhou 221002, PR China.

Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China.

出版信息

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

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) (PPS), which scavenged ROS and converted to poly(propylene sulfoxide) 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.

摘要

活性氧(ROS)的过度产生和炎症是噪声性听力损失(NIHL)的两个关键发病机制,这会导致外毛细胞(OHC)损伤和听力损失。在这项工作中,我们成功地开发了 ROS 响应性纳米粒子作为小檗碱(BBR)载体(PL-PPS/BBR),用于 NIHL 的 OHC 靶向治疗:Prestin 靶向肽 2(PrTP2)修饰的纳米粒子(PL-PPS/BBR),其有效地在 OHC 区域积聚,聚(丙烯硫醚)(PPS)在 ROS 环境中清除 ROS 并转化为聚(丙烯亚砜),以崩解并引发具有抗炎和抗氧化作用的 BBR 的快速释放。在这项研究中,证实了 PL-PPS/BBR 具有令人满意的抗炎和抗氧化作用。免疫荧光和扫描电子显微镜(SEM)图像表明,PL-PPS/BBR 有效地积聚在外毛细胞中,并保护外毛细胞的形态完整性。听觉脑干反应(ABR)结果表明,PL-PPS/BBR 可显著改善噪声暴露后 NIHL 豚鼠的听力。这项工作表明,PL-PPS/BBR 可能是一种具有临床应用前景的治疗与噪声相关损伤的新方法。

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