Near-Infrared Light-Triggered Thermosensitive Liposomes Modified with Membrane Peptides for the Local Chemo/Photothermal Therapy of Melanoma.

Abstract

PurposeA near-infrared (NIR)-triggered trans-activating transcriptional activator (TAT)-based targeted drug delivery system for the combined chemo/photothermal therapy of melanoma, namely, TAT-TSL-TMZ (temozolomide)/IR820, was developed for the first time.MethodsTAT-TSL-TMZ/IR820 liposomes were synthesized via thin-film dispersion and sonication. IR820 and TMZ were encased in the inner layer and lipid bilayer of the liposomes, respectively.ResultsDynamic light scattering results showed that the liposomes had an average hydrodynamic size of 166.9 nm and a zeta potential of −2.55 mV. The encapsulation rates of TMZ and IR820 were 35.4% and 28.6%, respectively. The heating curve obtained under near-infrared (NIR) laser irradiation showed that TAT-TSL-TMZ/IR820 liposomes had good photothermal conversion efficiency. The in vitro drug release curve revealed that NIR laser irradiation could accelerate drug release from TAT-TSL-TMZ/IR820 liposomes. The results of inverted fluorescence microscopy and flow cytometry proved that the uptake of TAT-TSL-TMZ/IR820 liposomes by human melanoma cells (MV3 cells) was concentration-dependent and that the liposomes modified with membrane peptides were more likely to be ingested by cells than unmodified liposomes. Confocal laser scanning microscopy indicated that TAT-TSL-TMZ/IR820 liposomes entered MV3 cells via endocytosis and was stored in lysosomes. In addition, TAT-TSL-TMZ/IR820 liposomes exposed to NIR laser showed 89.73% reduction in cell viability.ConclusionThis study investigated the photothermal conversion, cell uptake, colocation and chemo/photothermal effect of TAT-TSL-TMZ/IR820 liposomes.