Remotely Triggered Liposome Release by Near-Infrared Light Absorption via Hollow Gold Nanoshells

Abstract

An elusive goal for systemic drug delivery is to provide both spatial and temporal control of drug release. Liposomes have been evaluated as drug delivery vehicles for decades 1-5 , but their clinical significance has been limited by slow release or poor availability of the encapsulated drug 6 . Here we show that near-complete liposomal release can be initiated within seconds by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Our findings reveal that different coupling methods, such as having the HGNs tethered to, encapsulated within, or suspended freely outside the liposomes, all triggered liposomal release but with different levels of efficiency. For the underlying content release mechanism, our experiments suggest that microbubble formation and collapse due to the rapid temperature increase of the HGN is responsible for liposome disruption, as evidenced by the formation of solid gold particles after NIR irradiation and the coincidence of a laser power threshold for both triggered release and pressure fluctuations in the solution associating with cavitations. These effects are similar to those induced by ultrasound and our approach is conceptually analogous to use optically triggered nano-"sonicators" deep inside the body for drug delivery. We expect HGNs can be coupled with any nanocarriers to promote spatially and temporally controlled drug release. In addition, the capability of external HGNs to permeabilize lipid membranes can facilitate the cellular uptake of macromolecules, including proteins and DNA and allow for promising applications in gene therapy.One major challenge for current drug delivery is to control the drug release both spatially and temporally. Liposomes have been evaluated as drug delivery vehicles for decades 1-5 , but their clinical significance has been limited by slow release or poor availability of the encapsulated drug 6 . Here we show that near-complete liposomal release can be initiated within seconds ("burst" kinetics) by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Tissues are relatively transparent to NIR light which penetrates into body up to 10 cm 7 . This allows these HGN/liposome complexes to be addressed non-invasively within a significant fraction of the human body. Our findings on the underlying release mechanism reveal that this approach is conceptually analogous to using optically triggered nano-"sonicators" deep inside the body for drug delivery. Email: gorilla@engineering.ucsb Liposomes optimized to be highly stable and resistant to drug leakage in the circulation 8,9 are hampered by suboptimal drug release to serve as drug carriers. Current endogenous strategies in drug release have focused on incorporating components into liposomes to achieve either thermal, pH, enzymatically triggered or receptor-targeted liposomes 3-5 , however, none of them has led to marketed drugs 10 . It is difficult to include a destabilizing agent into the liposomes to promote release without compromising their ...

Interfacing Zwitterionic Liposomes with Inorganic Nanomaterials: Surface Forces, Membrane Integrity, and Applications

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