Synergistic Chemo-Photothermal Suppression of Cancer by Melanin Decorated MoOx Nanosheets

Two-dimensional (2D) nanomaterials able to effectively absorb near-infrared (NIR) radiation have shown considerable potential as multifunctional platforms in the treatment of cancer. Here, we report a molybdenum dioxide (MoOx)-based system for synergistic chemo- and photothermal therapy of cancer. MoOx nanosheets were generated via a one-step hydrothermal route, grafted with poly(ethylene glycol) (PEG), and decorated with melanin (Mel), with successful functionalization confirmed by IR spectroscopy. The mean diameter and thickness of the MoOx particles were found to be 302 ± 34 nm and 19 ± 2 nm using atomic force microscopy. The hydrodynamic size of the MoOx nanosheets was 105 ± 17 nm, and the resulting final MoOx-PEG-Mel-DOX nanocomposite formulation had a uniform diameter of 161 ± 26 nm. The MoOx-PEG-Mel nanosheets efficiently convert NIR light to heat, possessing a photothermal conversion efficiency of 61.7%. They can also be loaded with doxorubicin hydrochloride (DOX), giving a high drug loading (325.6 mg DOX/g MoOx-PEG-Mel). DOX release from the formulation is influenced by both pH and NIR irradiation. Systematic in vitro and in vivo evaluations reveal that synergistic chemo- and photothermal therapy using MoOx-PEG-Mel-DOX can completely eradicate a tumor with no observable off-target cytotoxicity. This is the first report of the fabrication of enhanced photothermal agents by combining MoOx nanosheets and a natural product. This work proffers a strategy for efficiently treating cancer as well as potentially extending the photothermal applications of 2D nanomaterials by surface melanin functionalization.