Intracellular delivery and photothermal therapeutic effects of polyhistidine peptide-modified gold nanoparticles

Gold nanoparticles (AuNPs) are widely used as an agent in photothermal therapy (PTT) against various cancers. However, a drug delivery system (DDS) is required for effective PTT using AuNPs as AuNPs accumulate passively in tumors. In the present study, we used polyhistidine peptide, a novel cell-penetrating peptide, which is efficiently internalized into tumor cells, as a DDS carrier for PTT using AuNPs. Polyhistidine peptide-modified AuNPs are efficiently internalized into RERF-LC-AI human lung squamous cancer cells and localized to the intracellular lysosome, which is based on the nature of the polyhistidine peptide. Furthermore, the polyhistidine peptide-modified AuNPs inhibited proliferation of RERF-LC-AI cells in a polyhistidine peptide modification-dependent manner under 660nm laser irradiation. Quantitative real-time PCR showed increased expression levels of an apoptosis-related gene (bax) and heat stress-related gene (hsp70) in RERF-LC-AI cells treated with polyhistidine peptide-modified AuNPs and laser. Our findings highlight the efficacy of AuNPs modified with H16 peptide in PTT. •CGH16 peptide was used as a DDS carrier to develop tumor-selective AuNPs.•AuNPs-CGH16 are efficiently internalized into RERF-LC-AI human lung cancer cells.•AuNPs-CGH16 showed cytotoxicity to RERF-LC-AI cells under 660nm laser irradiation.•Cytotoxic mechanism of AuNPs-CGH16 was the induction of heat stress and apoptosis.•AuNPs-CGH16 shows human lung cancer cells-selective PTT efficacy.