Abstract
Precise control of drug release from nanoparticles can improve efficacy and reduce systemic toxicity associated with administration of certain medications. Here, we combined two phenomena, photothermal conversion in plasmon resonant gold coating and thermal sensitivity of liposome compositions, to achieve a drug delivery system that rapidly releases doxorubicin in response to external stimulus. Methods: Thermosensitive liposomes were loaded with doxorubicin and gold-coated to produce plasmon resonant drug delivery system. Plasmon resonance facilitates release of contents upon near-infrared laser illumination, thus providing spatial and temporal control of the process. This controlled delivery system was compared to thermosensitive liposomes without gold coating and to the FDA-approved Doxil that was gold-coated to create a plasmon resonant coating. Release of doxorubicin from the gold-coated thermosensitive liposomes was further confirmed by tests of cell viability. Results: Upon laser illumination at 760 nm and 88 mW/cm(2) power density, permeability of plasmon resonant liposomes increased by three orders of magnitude, from 70×10(-12) to 60,000x10(-12) cm/s. In control experiments, mild hyperthermia (42°C) increased permeability of these thermosensitive liposomes to just 3,700×10(-12) cm/s. Neither hyperthermia nor laser illumination elicit content release from Doxil or plasmon resonant Doxil obtained by gold coating. Laser-induced release of doxorubicin from plasmon resonant thermosensitive liposomes resulted in the loss of cell viability significantly greater than in any of the control groups. Conclusion: Combination of thermosensitive liposomes with plasmon resonant coating enables rapid, controlled release, not currently available in pharmaceutical formulations of anticancer drugs.