TAT Peptide-Functionalized Gold Nanostars: Enhanced Intracellular Delivery and Efficient NIR Photothermal Therapy Using Ultralow Irradiance

Gold nanoparticles have great potential in plasmonic photothermal therapy (photothermolysis), but their intracellular delivery and photothermolysis efficiency have yet to be optimized. We show that TAT-peptide-functionalized gold nanostars (NS) enter cells significantly more than bare or PEGylated NS. The cellular uptake mechanism involves actin-driven lipid raft-mediated macropinocytosis, where particles primarily accumulate in macropinosomes but may also leak out into the cytoplasm. After 4-h incubation of TAT-NS on BT549 breast cancer cells, photothermolysis was accomplished using 850 nm pulsed laser under 0.2 W/cm2 irradiation, below the maximal permissible exposure of skin. These results demonstrate the enhanced intracellular delivery and efficient photothermolysis of TAT-NS, promising agents in cancer therapy.