Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA

Area of Science:

• Biotechnology
• Gene Therapy
• Nanotechnology

Background:

• Ultrasound combined with microbubbles (sonoporation) shows promise for gene delivery due to low toxicity and ease of in vivo application.
• Current methods using free plasmid DNA (pDNA) and microbubbles exhibit low in vivo gene transfer efficiency, attributed to pDNA degradation and low local concentrations.

Purpose of the Study:

• To develop enhanced microbubbles for improved DNA binding, protection, and in vivo delivery in ultrasound-mediated gene transfer.
• To investigate the efficacy of polymer-coated microbubbles in protecting DNA from degradation and enhancing its stability.

Main Methods:

• Albumin-shelled microbubbles were coated with poly(allylamine hydrochloride) (PAH) to create a cationic surface.
• The ability of coated microbubbles to bind pDNA and protect it from nuclease degradation was assessed.
• The effect of the PAH coating on microbubble size, ultrasound responsiveness, injectability, and in vivo half-life was evaluated.

Main Results:

• Polymer-coated microbubbles demonstrated the ability to bind significant amounts of pDNA (up to 0.1 pg/microbubble).
• The cationic coating effectively protected the bound DNA from enzymatic degradation.
• PAH coating increased microbubble stability, with a half-life of approximately 7 hours, enhancing in vivo applicability.
• Coating did not significantly alter microbubble size or ultrasound responsiveness.

Conclusions:

• Layer-by-layer (LbL) coated microbubbles offer a novel approach for binding and protecting DNA for ultrasound-mediated gene delivery.
• These enhanced microbubbles show potential to overcome limitations of current sonoporation techniques, improving in vivo gene transfer efficiency.
• The development represents a significant step forward in the field of ultrasound-targeted gene therapy.