Polyplex-microbubble hybrids for ultrasound-guided plasmid DNA delivery to solid tumors

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Molecular Imaging

Background:

• Microbubble ultrasound contrast agents are emerging as potential in vivo gene carriers.
• Targeted gene delivery remains a significant challenge in therapeutic applications.

Purpose of the Study:

• To synthesize and evaluate novel polyplex-microbubbles for enhanced systemic circulation and tumor transfection.
• To investigate the impact of surface modification on microbubble properties and DNA loading capacity.

Main Methods:

• Branched polyethylenimine (PEI) was modified with polyethylene glycol (PEG) and attached to lipid-coated microbubbles.
• Pharmacokinetic modeling was used to analyze in vivo circulation and adhesion.
• Ultrasound was applied over implanted tumors for site-specific gene delivery using DNA/PEI-microbubbles.

Main Results:

• Polyplex-microbubbles demonstrated improved circulation and reduced nonspecific adhesion compared to PEI-microbubbles.
• Ultrasound-guided delivery resulted in over 10-fold higher tumor bioluminescence.
• Ex vivo analysis showed >40-fold higher gene expression in sonicated tumor tissue.

Conclusions:

• The polyplex-microbubble platform offers controlled DNA loading and packaging for ultrasound-guided tissue transfection.
• This technology shows promise for targeted gene therapy applications.