Targeted carbon monoxide delivery combined with chemodynamic, chemotherapeutic and photothermal therapies for enhanced antitumor efficacy

Abstract

Traditional chemotherapy is considered an indispensable clinical treatment modality because of its high efficiency, but its effectiveness is hindered by its shortcomings such as high side effects, poor selectivity and multidrug resistance, which can be alleviated by combining with some emerging cancer treatment modalities. Herein a multifunctional nanoplatform HMCuS@DHA@PDA@MnCO@FA (HDPMF) was prepared, where polydopamine-coated hollow mesoporous copper sulfide (HMCuS@PDA) was taken as the carrier with its surface covalently functionalized by a carbon monoxide (CO) releasing molecule (MnCO) and folic acid (FA) directing group, and a chemotherapeutic drug dihydroartemisinin (DHA) was also loaded within its hollow cavity. HDPMF selectively targeted folate receptor (FR) overexpressed cancer cell lines to which DHA and CO were delivered in the tumor microenvironment (acidic with H₂O₂ overproduction) upon 808 nm near-infrared (NIR) light irradiation. Meanwhile, the HMCuS@PDA core endowed HDPMF with an obvious photothermal effect and the ability to trigger decomposition of overexpressed H₂O₂ through a Fenton-like reaction to generate highly toxic hydroxyl radical (˙OH) species. In vitro cytotoxicity evaluation disclosed that HDPMF showed prominent anticancer effects with a relatively low IC₅₀ value (<15 μg mL⁻¹) under 808 nm NIR light irradiation, and it presented very low cytotoxicity toward normal cells under dark conditions. Thus, combined with gas therapy, photothermal therapy, chemodynamic therapy, and chemotherapy, the nanoplatform HDPMF may offer implications for effective multimodal antitumor therapies.