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Smart drug delivery systems represent state-of-the-art approaches for targeted therapy of life-threatening diseases such as cancer and cardiovascular diseases. Stimuli-responsive on-demand release of therapeutic agents at the diseased site can significantly limit serious adverse effects. In this study, we engineered a near-infrared (NIR) light-responsive liposomal gold nanorod-containing platform for on-demand delivery of proteins using a hybrid formulation of ultrasmall gold nanorods (AuNRs), thermosensitive phospholipid (DPPC) and non-ionic surfactant (Brij 58). In light-triggered release optimization studies, 55.6% (+/-4.8) of a FITC-labelled model protein, ovalbumin (MW 45kDa) was released in 15min upon NIR irradiation (785nm, 1.35W/cm(2) for 5min). This platform was then utilized to test on-demand delivery of urokinase-plasminogen activator (uPA) for bleeding-free photothermally-assisted thrombolysis, where the photothermal effect of AuNRs would synergize with the released uPA in clot lysis. Urokinase light-responsive liposomes showed 80.7% (+/- 4.5) lysis of an in vitro halo-clot model in 30min following NIR irradiation (785nm, 1.35W/cm(2) for 5min) compared to 36.3% (+/- 4.4) and 15.5% (+/- 5.5) clot lysis from equivalent free uPA and non-irradiated liposomes respectively. These results show the potential of low-dose, site-specific thrombolysis via the combination of light-triggered delivery/release of uPA from liposomes combined with photothermal thrombolytic effects from gold nanorods. In conclusion, newly engineered, gold nanorod-based, NIR light-responsive liposomes represent a promising drug delivery system for site-directed, photothermally-stimulated therapeutic protein release.
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