ROS-Responsive Nanoparticle as a Berberine Carrier for OHCTargeted Therapy of Noise-Induced Hearing Loss
ROS-Responsive Nanoparticle as a Berberine Carrier for OHCTargeted Therapy of Noise-Induced Hearing Loss
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ROS 响应纳米颗粒作为小檗碱载体用于 OHCT 噪声性听力损失靶向治疗
DOI：
10.1021/acsami.0c21151
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
刘洪梅
中科院分区：
文献类型：
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作者：
赵泽祺;韩正中;Konduru Naveena;雷冠雄;邱士伟;李轩毅;李婷;时晰;庄伟;李雅兰;乔月华;刘洪梅
噪声性听力损失（noise-induced hearing loss，NIHL）的两个重要发病机制是活性氧（reactive oxygen species，ROS）的过度产生和炎症反应，从而导致外毛细胞（outer hair cell，OHC）损伤和听力损失。在这项工作中，我们成功地开发了ROS响应纳米颗粒作为黄连素（BBR）载体（PLPPS/BBR）用于NIHL的OHC靶向治疗：Prestin靶向肽2修饰纳米粒（PL-PPS/BBR），有效地积累在OHC地区，和聚（硫化丙烯）120（PPS 120），清除活性氧并转化为聚（丙烯亚砜）120在ROS环境中分解并引发具有抗炎和抗氧化作用的BBR的快速释放。本研究证实了PL-PPS/BBR具有良好的抗炎和抗氧化作用。免疫荧光和扫描电子显微镜（SEM）图像显示，PL-PPS/BBR有效地积累在OHC和保护OHC的形态完整性。听性脑干反应（ABR）结果表明，PL-PPS/BBR显着改善噪声暴露后NIHL豚鼠的听力。本工作表明，PL-PPS/BBR可能是一种新的潜在的治疗噪声相关损伤的临床应用。
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 (PLPPS/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. Immuno-fluorescence 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.