Hollow Copper\nSulfide Nanocubes Loaded with Pt(IV)\nComplexes for Cancer Multimodal Therapy

Chemotherapy (CT) can significantly inhibit tumor growth,\nmetastasis,\nand recurrence during cancer therapy. People have widely used platinum\ndrugs in cancer treatment. However, as most chemotherapeutic drugs,\nplatinum drugs still have shortcomings such as poor solubility, low\ncell uptake, nonspecific distribution, multidrug resistance, and adverse\nside effects. Therefore, we synthesized hollow copper sulfide (CuS)\nnanocubes with photothermal and photodynamic properties as carriers\nfor Pt(IV) drugs. Hollow CuS nanocubes have attracted considerable\ninterest in the field of cancer photothermal therapy (PTT) using multiple\nbiological windows. Under near-infrared (NIR) laser irradiation, Cu<sup>2+</sup> can be reduced into Cu<sup>+</sup> in the presence of hydrogen\nperoxide in the tumor microenvironment. The resulting Cu<sup>+</sup> can be used for photodynamic therapy (PDT), which can perform a\nFenton-like reaction under acidic conditions (pH 5.5–6.5) and\ncatalyze hydrogen peroxide to produce ·OH in the tumor microenvironment.\nIn addition, compared with Pt(II) drugs, Pt(IV) drugs not only have\nlower systemic toxicity but also consume glutathione (GSH), thereby\nincreasing reactive oxygen species (ROS) levels in tumor cells and\neffectively promoting PDT. In this study, we oxidized ethylenediamine\nplatinum chloride to its tetravalent state, loaded the Pt(IV) complexes\nusing hollow CuS nanocubes, and modified the surfaces of the nanoparticles\nwith PEG to improve the EPR effect. The Pt(IV)-loaded hollow CuS nanocubes\nmodified with PEG (Pt(IV)-CuS@PEG) are expected to be used for tumor\nchemo/photothermal/photodynamic therapy.