Non-stoichiometric cobalt sulfide nanodots enhance photothermal and chemodynamic therapies against solid tumor

Photodynamic therapy (PDT) mainly relies on reactive oxygen species generated by light- activated photosensitizers and oxygen to kill tumor cells. However, a critical limitation of the current PDT is that it is less effective in solid tumors where the microenvironment is hypoxic, and, therefore, repeated treatment is required. Here, non-stoichiometric Co_2.19S₄ nanodots (NDs), which can be rapidly degraded to cobalt (Co²⁺) and sulfur (S^2-) ions, were developed to enhance tumor photothermal therapy (PTT) and chemodynamic therapy (CDT) via the capture of copper (Cu²⁺) ions (starvation therapy) in the hypoxic tumor microenvironment under near-infrared irradiation. Co_2.19S₄ NDs with excellent photothermal conversion efficiency (ɳ = 52%) can be used for PTT, and the Co²⁺ ions produced by their degradation can catalyze the endogenous hydrogen peroxide of tumor cells to produce highly toxic hydroxyl radicals to achieve tumor CDT. The mechanism of starvation therapy was explored using western blotting, and the results indicated that blocking the uptake of Cu²⁺ ions could restrain the growth and proliferation of tumors by inhibiting the BRAF/mitogen-activated extracellular signal regulated kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway. Our work highlights the great potential of Co_2.19S₄ NDs as a theranostic agent for implementing photoacoustic/photothermal imaging and starvation therapy-enhanced PTT/CDT.