Tumor Microenvironment-Regulated Redox Responsive Cationic Galactose-Based Hyperbranched Polymers for siRNA Delivery

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• The tumor microenvironment presents unique challenges for drug and gene delivery.
• Developing targeted and efficient delivery systems is crucial for cancer therapy.
• Redox-sensitive polymers offer potential for controlled release in the tumor microenvironment.

Purpose of the Study:

• To synthesize and characterize redox-responsive galactose-based hyperbranched polymers (HRRP).
• To evaluate the efficacy of HRRP for siRNA delivery and gene silencing in cancer cells.
• To assess the biocompatibility and stability of HRRP-based polyplexes.

Main Methods:

• Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to prepare HRRP with varying molecular weights and LAEMA:AEMA ratios.
• Polyplex formation with siRNA was analyzed.
• Cellular internalization and gene silencing (EGFR) were evaluated in HeLa cancer cells.
• Biocompatibility was assessed using normal cell lines and cell viability assays.

Main Results:

• HRRP demonstrated glutathione (GSH) responsiveness, regulating cellular uptake and siRNA release.
• Nanosized polyplexes were formed with 10 kDa HRRP (L:A ratio 1.5).
• Approximately 85% EGFR silencing was achieved in HeLa cells with high cell viability (>95%).
• Polyplexes exhibited excellent stability in serum and low cytotoxicity.

Conclusions:

• Redox-responsive galactose-based cationic hyperbranched polymers are effective for siRNA delivery.
• The developed HRRP system shows promise for targeted gene silencing in cancer.
• These polymers warrant further investigation for preclinical gene therapy applications.