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

TLDR

Gold nanoparticles hold promise for plasmonic photothermal therapy, yet their intracellular delivery and photothermolysis efficiency remain suboptimal. TAT‑functionalized gold nanostars enter cells via actin‑driven, lipid‑raft–mediated macropinocytosis, accumulating in macropinosomes and occasionally leaking into the cytoplasm, and after 4‑h incubation on BT549 breast cancer cells, 850‑nm pulsed laser irradiation at 0.2 W/cm² achieved photothermolysis below skin exposure limits. TAT‑peptide‑functionalized gold nanostars deliver more efficiently into cells than bare or PEGylated counterparts and, under low‑irradiance 850‑nm pulsed laser, achieve efficient photothermolysis, indicating their promise for cancer therapy.

Abstract

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/cm(2) 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.