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

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 (PPS 120 ), 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.

β-Cyclodextrin and Oligoarginine Peptide-Based Dendrimer-Entrapped Gold Nanoparticles for Improving Drug Delivery to the Inner Ear

“…Moreover, a recent anatomical study of the human cochlea revealed that perforated structures at the modiolar surface of the scala tympani (ST) and the scala vestibuli (SV) allowed fluid exchanges between the modiolar space/vascular tree, the perilymph, and the spiral ligament ( Rask-Andersen et al, 2006 ). Our nanoparticles, with a diameter of 5 nm, are much smaller than those used in other experiments (diameter >200 nm) ( Zhao et al, 2021 ). These results suggest that the size of nanoparticles affects absorption, and drugs with a small size in the perilymph reach the modiolus or limbus more easily.…”

“…The loading content (%) and loading efficiency (%) of Au-DENPs-Dex were measured by high-performance liquid chromatography [HPLC (Thermo Fisher U3000)] at following time points: 0.5, 1, 3, 5, 8, 24, 48, and 72 h ( Yoon et al, 2015 ). The test conditions were as follows: a series of Dex solutions with different concentrations (1,000, 500, 250, 125, 62.5, 31.25, 15.6, 7.8, and 3.9 μg/m L), a mobile phase of water and acetonitrile (60:40 v/v), sample injection volume of 20 μL, flow rate of 1.0 ml/min, column temperature of 30°C, and detection wavelength of 240 nm ( Zhao et al, 2021 ).…”

“…The HEIOC1 cells were treated with the fresh complete medium with various concentrations of SM (0, 1, 2, 5, 10, 15, 20, 30, and 40 mg/ml) to determine the optimal dosing concentration of SM. In another 96-well plate, the HEIOC1 cells were dealt with the best dosing concentration of SM after pretreatment with six different concentrations (1, 5, 10, 15, 20, and 30 μg/ml) of Au-DENPs-Dex and Dex alone; 0.01 M PBS was used as the control group ( Zhao et al, 2021 ). Then, the cytotoxicity of SM to HEIOC1 and the efficacy of free Dex and Au-DENPs-Dex in treating SM ototoxicity were quantitatively detected by the CCK-8 method to verify drug delivery efficiency of nanoparticles.…”

Reactive Oxygen Species (ROS)-Responsive Biomaterials for the Treatment of Bone-Related Diseases

“…(C) PPS 120 converted to poly(propylene sulfoxide) 120 and released drug in an ROS environment. Reproduced with permission ( Zhao et al, 2021 ). Copyright 2021 American Chemical Society.…”

“…When simulated the ROS environment with 1 mM H 2 O 2 , a fast release of berberine (BBR) was observed from PL-PPS/BBR at 48 h ( Figure 2C ). During this progress, PPS 120 scavenged ROS and converted to poly(propylene sulfoxide) 120 when reacted with ROS to obtain the rapid release of BBR ( Zhao et al, 2021 ). Thioether-containing polymers contribute an effective method for loading and delivering hydrophobic drugs especially for the application of cancer therapy.…”