Tunable PEGylation platform for efficient siRNA delivery using mesoporous silica nanoparticles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Poly(ethylene glycol) (PEG) coatings are crucial for nanoparticle stability and biocompatibility.
• Conventional PEGylation methods are complex, limiting reproducibility and control over charge-shielding balance for siRNA delivery.

Purpose of the Study:

• To develop a composition-tunable PEGylation strategy using poly(DMAEMA-co-PEGMA) copolymers for efficient siRNA delivery.
• To optimize copolymer ratios and PEG chain lengths for enhanced nanoparticle performance.

Main Methods:

• Synthesized poly(2-(dimethylamino)ethyl methacrylate-co-poly(ethylene glycol) methacrylate) (poly(DMAEMA-co-PEGMA)) copolymers via one-step free-radical polymerization.
• Formulated complexes with mesoporous silica nanoparticles (MSNs) and varying copolymer compositions.
• Evaluated siRNA loading, colloidal stability, serum resistance, cytocompatibility, cellular uptake, and gene silencing efficacy.

Main Results:

• Optimized MSN/copolymer complexes demonstrated enhanced siRNA loading and superior colloidal stability.
• The PEGylation strategy provided significant serum resistance and maintained favorable cytocompatibility.
• Cellular studies confirmed improved uptake and effective PD-L1 gene silencing.

Conclusions:

• Established a composition-tunable and scalable PEGylation platform for nanoparticle surface modification.
• Overcame limitations of conventional methods, offering a promising strategy for siRNA-based therapeutics.
• Demonstrated efficient delivery of PD-L1 siRNA using the novel copolymer approach.