Back to Search Start Over

ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases.

Authors :
Elbedwehy, Ahmed M.
Wu, Jun
Na, Hee-Kyung
Baek, Ahruem
Jung, Haejin
Kwon, Ik Hwan
Lee, Sang Won
Kim, Jeong Hun
Lee, Tae Geol
Source :
Journal of Controlled Release. Sep2024, Vol. 373, p224-239. 16p.
Publication Year :
2024

Abstract

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w /w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to −25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model. The study discusses the development of a novel drug delivery system utilizing charge reversal mesoporous silica nanoparticles (MSNs) for the treatment of neovascular retinal diseases. [Display omitted] • Mesoporous Silica Nanoparticles' surface charge was delicately adjusted for reversal under ROS-response. • Intravitreal injection of Ar-MSNs-TK-PEG was immobilized in the mouse vitreous; however, under oxidative stress, the surface charge reversed, facilitating nanoparticle diffusion. • HN loaded Ar-MSNs-TK-PEG provides protection against oxidative stress-induced apoptosis, evidenced by reduced TUNEL and caspase3 activation. • Intravitreal injection of HN-loaded Ar-MSNs-TK-PEG inhibit retinal neovascularization in a mice model of oxygen-induced retinopathy without inducing toxicity in retinal tissues. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01683659
Volume :
373
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
179498468
Full Text :
https://doi.org/10.1016/j.jconrel.2024.07.022