Cancer-targeting gold-decorated melanin nanoparticles for in vivo near-infrared photothermal therapy†

Photothermal cancer therapy has gained increasing attention as a minimally invasive treatment via the localized heating of photothermal agents to eradicate cancer cells. However, its clinical translation has been limited by insufficient photothermal conversion in the near-infrared (NIR) range and low tumor-targeting efficiency. Here, synthetic melanin-like nanoparticles (∼190 nm in diameter) decorated with a cluster of smaller gold nanoparticles (∼20 nm in diameter) are developed as efficient NIR photothermal agents for in vivo cancer treatment. The melanin-gold hybrid nanoparticles are prepared by the oxidative polymerization of dopamine into colloidal melanin-like nanoparticles, followed by the spontaneous reduction of gold ion precursors into plasmonic nanoparticles on the surface of melanin nanoparticles. The gold nanoparticles significantly increase the NIR light absorption and photothermal conversion of the melanin nanoparticles, making their overall photothermal performance superior to conventional gold nanorods. Chemical conjugation of epidermal growth factor to the hybrid nanoparticles facilitates their cellular internalization into lung adenocarcinoma cells and enables in vivo tumor-targeting in a xenograft mouse model. The nanoparticles also exhibit excellent dispersion stability in serum and maintain high photothermal efficiency even after extensive laser irradiation. Our results suggest that the electronic hybridization of melanin and gold nanostructures provides a new opportunity to fine-tune their optical and chemical properties for tumor-targeted photothermal therapy.