Controlled Near Infrared Laser-Activated Liposome Release

Abstract

Liposomes have been evaluated as drug delivery vehicles for decades. However, it is hard to prepare liposomes to both balance enhanced drug retention and rapid and targeted content release. The challenge is to initiate the release of encapsulated drugs at the diseased site at a controlled rate. We recently developed a novel photo-activated approach by which near-complete contents release from liposomes can be completed within seconds by irradiating encapsulated or tethered hollow gold nanoshells (HGN) with a near infrared (NIR) pulsed laser. The rapid heating of the gold nanoshells leads to unstable microbubble formation and collapse, the same type of cavitation events associated with ultrasound. Our approach is conceptually analogous to the use of optically triggered nano-“sonicators” deep inside the body for drug delivery. We demonstrate that even though the local temperature surrounding HGNs can be very high, the bulk temperature of the solution only rises by ∼1°C. Results from electrophoresis and quantitative PCR all show no damage to DNA molecules mixed with HGNs after NIR irradiation. These results confirm the potential of using this optical approach to permeabilize lipid membranes and facilitate the cellular uptake of DNAs for gene therapy. Since DNAs are relatively robust macromolecules, we also investigated the more delicate dye molecule, carboxyfluorescein (CF), which contains a double bond; liquid chromatography followed by mass spectral analysis shows that ∼95% of CF molecules are intact. These results agree well with our hypothesis that only an few nanometer thick layer surrounding HGNs reach temperatures above the explosive boiling temperature (∼ 650 K), so that only CF molecules close to HGNs are damaged. Other NIR responsive materials, such as carbon nanotubes and solid gold nanoparticles were used as triggering agent for liposome release, and their release efficiencies are compared with those of HGNs.