Engineering Cu2−xS-conjugated upconverting nanocomposites for NIR-II light-induced enhanced chemodynamic/photothermal therapy of cancer

The integration of chemodynamic therapy (CDT) and photothermal therapy (PTT) has played a huge role in improved anticancer treatments. Here, a novel multifunctional nanoplatform based on Cu2−xS conjugated NaYF4:Yb/Er@NaYF4:Yb upconversion nanoparticles (UCNPs) was proposed and designed. In the UCNPs–Cu2−xS nanocomposites, UCNPs with excellent luminescent properties and a high X-ray attenuation coefficient can serve as an upconversion luminescence (UCL) and computer tomography (CT) imaging contrast agent; meanwhile, Cu(II) in the Cu2−xS nanodots enables the nanocomposites to have a magnetic resonance imaging (MRI) ability owing to the presence of unpaired electrons. Moreover, the Cu2−xS nanodots with a strong absorbance in the NIR II biowindow not only could be employed as a stable photothermal agent under NIR laser irradiation, but also could be used as a photothermal-enhanced Fenton nanocatalyst to respond to over-expressed H2O2 in the tumor microenvironment (TME) and generate toxic hydroxyl radicals (˙OH) to effectively kill cancer cells. Furthermore, the UCNPs–Cu2−xS nanocomposites possess negligible cytotoxicity and a high photothermal conversion efficiency (43.8%) in the NIR-II biowindow (1064 nm), indicating that they possess great potential for the UCL/CT/MR multi-modal imaging guided synergistic enhanced CDT/PTT of cancer.