Near-infrared light-responsive liposomes for protein delivery: Towards bleeding-free photothermally-assisted thrombolysis

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 (Brij58). In light-triggered release optimization studies, 55.6% (+/- 4.8) of a FITC-labelled model protein, ovalbumin (MW 45 kDa) was released in 15 min upon NIR irradiation (785 nm, 1.35 W/cm(2) for 5 min). 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 30 min following NIR irradiation (785 nm, 1.35 W/cm(2) for 5 min) 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.

Automated summary

Smart drug delivery systems utilizing near-infrared light-responsive liposomal gold nanorods show potential for targeted therapy of cancer and cardiovascular diseases with minimal adverse effects. This novel platform combines light-triggered protein release with photothermal thrombolytic effects for site-specific thrombolysis, offering a promising approach for advanced medical treatment.