(5dg) Liposomal Nanomedicine: Multi-Compartment Structure and Remotely Triggered Release

My research has been focusing on exploring the relations between structure, composition and function in biomembranes at the molecular scale. Combining nanotechnologies and employing biomaterials, my ultimate goal is to develop ?nanomedicine?, aiming at early and accurate diagnoses as well as effective targeted therapy.

For example, sub-micron liposome-based nanoparticles encapsulating therapeutic agents represent one of the most advanced classes of drug delivery systems. However, currently marketed drug delivery systems lack the abilities of both good drug retention and the active release of the carried drug. To address these challenges, we learn from nature and have constructed a multi-compartment structure consisting of drug-loaded liposomes encapsulated within another bilayer, similar to the multicompartment structure in eukaryotic cells. These liposome-based complex carriers have excellent retention of the encapsulated drug, protect the drug during circulation, prevent it from reaching healthy tissues, and permit its accumulation at the disease sites. To achieve controlled drug release, it is not feasible to rely on passive diffusion or slow non-specific degradation of the liposomal carrier. We report a novel photo-activated approach where near-complete contents release from liposomes can be initiated within seconds by irradiating hollow gold nanoshells (HGN) with a near infrared (NIR) pulsed laser. The HGNs were encapsulated within, tethered to, or suspended freely with liposomes. NIR light can penetrate up to 10 cm into the tissue, which would allow this approach to apply non-invasively within a significant fraction of the human body. The mechanisms of this triggered release is that absorbing NIR causes the HGNs to rapidly increase in temperature, leading to the formation of microbubbles whose collapse causes transient membrane rupture and content release. Therefore, this remotely triggered release is analogous to using optically triggered nano-?sonicators? deep inside the body to initiate drug release.

The research on liposomal nanomedicine has the potential to advance drug delivery for conventional anticancer treatments as well as gene-delivery, immunostimulatory, and gene-silencing applications using new genetic drugs (plasmid DNA?containing therapeutic genes, antisense oligonucleotides, and small, interfering RNA [siRNA]).