(734e) Size Effect of Hollow Gold Nanoparticles on Photo-Activated Drug Release of a Liposomal Carrier

Liposome drug delivery systems are faced by the quandary of minimizing non-specific drug release and initiating fast release at the site of interest.  A novel strategy is to separate the mechanism of drug release from drug retention by using an external agent to trigger drug release.   Near infra-red (NIR) light is an appropriate choice as it is physiologically friendly with minimal thermal injury to normal tissues and light penetration of several cm. We can synthesize Hollow Gold Nanoparticles (HGN) to absorb NIR light over the range from 700-900 nm by manipulating the diameter to shell thickness ratio. NIR picosecond pulsed laser light absorbed by liposome encapsulated or tethered HGN is rapidly converted into thermal energy; the large temperature gradients lead to the formation of transient vapor nanobubbles in aqueous solution. The collapse of the nanobubbles ruptures cell, endosome, or liposome membranes; thereby releasing their contents with minimal damage to the contents or surroundings.  We find smaller (10 – 15 nm) HGN show higher specific absorbance of NIR light than larger (30-50 nm) HGN, which leads to more efficient membrane rupture and delivery of liposome contents. We have systematically synthesized monodisperse HGN of sizes from 10 – 40 nm and determined the relative efficacy of laser power and duration on the rate of contents release from 200 nm liposomes. A fluorescent dye was encapsulated within a liposome as a model agent to study release kinetics triggered by a picosecond pulsed NIR laser irradiation of the HGN coupled to the liposome. Subsequently, an anticancer drug was encapsulated within the liposomes to deliver the drug to prostate cancer cell in vitro; near-complete cell killing was observed. The study provides design parameters for engineering drug delivery systems that ultimately will be apply to tumor targeting therapeutics.