In vivo tumor transfection mediated by polyplexes based on biodegradable poly(DMAEA)-phosphazene

Area of Science:

• Biomaterials Science
• Gene Therapy
• Nanotechnology

Background:

• Non-viral gene delivery systems are crucial for safe and effective gene therapy.
• Biodegradable polymers offer advantages over non-biodegradable counterparts for in vivo applications.
• Poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz) is a novel biodegradable polymer developed for gene delivery.

Purpose of the Study:

• To evaluate the biodistribution and in vivo transfection efficiency of p(DMAEA)-ppz polyplexes.
• To compare the performance of p(DMAEA)-ppz polyplexes with non-biodegradable polyethylenimine (PEI 22kDa) polyplexes.
• To assess the potential of p(DMAEA)-ppz for targeted gene delivery to tumors.

Main Methods:

• Intravenous administration of plasmid DNA polyplexes (p(DMAEA)-ppz and PEI 22kDa) into tumor-bearing mice.
• Biodistribution studies were conducted to track polyplex clearance and organ accumulation.
• In vivo gene expression levels were quantified using a reporter gene assay.

Main Results:

• Both p(DMAEA)-ppz and PEI 22kDa polyplexes were rapidly cleared from circulation and accumulated in the liver and lungs.
• Significant tumor accumulation (5-8% ID/g) was observed for both polyplex systems at 240 minutes post-administration.
• p(DMAEA)-ppz polyplexes demonstrated substantial gene expression in tumors with minimal expression in other organs, unlike PEI 22kDa polyplexes.

Conclusions:

• p(DMAEA)-ppz polyplexes exhibit efficient tumor accumulation and reporter gene expression in vivo.
• The preferential gene expression in tumors by p(DMAEA)-ppz highlights its potential for targeted cancer gene therapy.
• p(DMAEA)-ppz represents a promising biodegradable non-viral vector for therapeutic gene delivery to tumors.