Gold cluster-labeled thermosensitive liposmes enhance triggered drug release in the tumor microenvironment by a photothermal effect.

Stimulus-triggered drug release based on the liposomal drug delivery platform has been studied vigorously to increase drug release at the target site. Although the delivery system has been developed, an effective carrier system is needed to achieve effective therapeutic efficacy. Therefore, we focused on the development of gold cluster bound thermosensitive liposomes (G-TSL), which are capable of triggered drug release when stimulated by external near-infrared (NIR) irradiation in the tumor microenvironment. The size of doxorubicin (DOX)-loaded G-TSL (DOX/G-TSL) was 171.5 ± 8.3 nm, and the efficiency of DOX encapsulation was up to 90%. The release of DOX from DOX/G-TSL was increased 70% by NIR irradiation (1.50 W/cm(2) for 0.5 min) compared to non-gold-coated TSL. Consequentially, the gold cluster on the TSL enabled the light-controlled DOX release through the photothermal conversion of the energy of NIR-absorbed light, leading to membrane destabilization. Cell cytotoxicity of DOX/G-TSL was also increased by their NIR irradiation-triggered DOX release compared to non-NIR-irradiated DOX/G-TSL. In addition, we demonstrated the therapeutic efficacy of DOX/G-TSL against the MDA-MB-231 tumor model. The NIR-irradiated DOX/G-TSL treatment showed greater therapeutic efficacy than that of the non-NIR-irradiated DOX/G-TSL and control (p<0.05). Taken together, DOX/G-TSL has the potential for remote-triggered drug release upon stimulation with NIR irradiation in the tumor microenvironment, and may be applied to a broad range of photothermal-based disease therapies.