Targeted drug and gene delivery by pulsed laser-induced photomechanical waves

Shunichi Sato

Targeted drug and gene delivery by pulsed laser-induced photomechanical waves

Shunichi Sato

National Defense Medical College Research Institute, Japan

: J Pharm Drug Deliv Res

Abstract

We have demonstrated highly site-selective gene transfer and transvascular drug delivery in rodents by using pulsed laser-induced pressure waves, which are called photomechanical waves (PMWs). A PMW is generated by irradiating a light-absorbing material with a nanosecond laser pulse. For gene transfer, PMWs were applied to tissue injected with plasmid DNA or siRNA, enabling efficient targeted gene transfer to various tissues in vivo. Gene therapy experiments were performed by using this method. Adhesion of grafted skin was accelerated by delivering hepatocyte growth factor plasmid DNA to the graft and recovery of motor function was enhanced by delivering siRNAs targeting the intermediate filament proteins to spinal cord injury in rats. We also found that PMWs could selectively enhance the permeability of blood vessels. An Evans blue (EB) solution was injected into the rat tail vein and a PMW(s) was applied to the skin, muscle and brain. We observed laser fluence-dependent extravasation of EB in the tissues that had been exposed to a PMW(s). Uptake of leaked EB into cells in the extravascular space was also observed in the targeted tissues, indicating the capability for site-specific transvascular drug delivery by using a PMW(s). The results for the brain indicated opening of the bloodÃ¢Â€Â“brain barrier. Since EB molecules are strongly bound with serum albumin in blood, this method can be applied to macromolecules. The method is currently being applied to gliomas in rats to enhance the delivery efficiency of an antitumor drug.