Hyaluronic acid-modified core-shell structured cationic nanocarriers for posterior segment gene therapy

Area of Science:

• Biomaterials Science
• Ophthalmology
• Nanotechnology

Background:

• Effective gene delivery to the posterior eye is crucial for treating neovascular AMD.
• Current methods face challenges in achieving efficient and targeted delivery.

Purpose of the Study:

• To develop and evaluate a novel core-shell nanocarrier for intravitreal gene delivery.
• To overcome ocular barriers and enhance therapeutic efficacy for posterior segment diseases.

Main Methods:

• A core-shell nanocarrier was engineered with a cationic PβAE dendrimer core, a biodegradable PLGA shell, and surface hyaluronic acid (HA).
• The nanocarrier (HA-P P/ND) was optimized for size, DNA encapsulation, and sustained release.
• In vitro studies assessed cellular uptake, endosomal escape, and transfection efficiency in ARPE-19 cells.
• In vivo studies evaluated the nanocarrier's efficacy in a laser-induced wet AMD mouse model.

Main Results:

• Optimized HA-P P/ND showed uniform size (~200 nm), high DNA encapsulation (98%), and sustained release.
• HA significantly enhanced cellular uptake, lysosomal escape, and transfection efficiency (4.3-fold increase).
• The delivered antiangiogenic gene suppressed VEGF by 48.5% and inhibited endothelial cell functions.
• Intravitreal HA-P P/ND administration reduced choroidal neovascularization (CNV) lesions by 68% in a mouse model.

Conclusions:

• The developed multifunctional nanocarrier effectively overcomes ocular gene delivery barriers.
• This non-viral platform offers a promising strategy for treating posterior segment diseases like neovascular AMD.