ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases.
J Control Release
; 373: 224-239, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39002796
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retinal Neovascularization
/
Reactive Oxygen Species
/
Silicon Dioxide
/
Nanoparticles
Limits:
Animals
/
Humans
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Países Bajos