CaCO3-encircled hollow CuS nanovehicles to suppress cervical cancer through enhanced calcium overload-triggered mitochondria damage

Abstract

Cervical cancer stands is a formidable malignancy that poses a significant threat to women's health. Calcium overload, a minimally invasive tumor treatment, aims to accumulate an excessive concentration of Ca²⁺ within mitochondria, triggering apoptosis. Copper sulfide (CuS) represents a photothermal mediator for tumor hyperthermia. However, relying solely on thermotherapy often proves insufficient in controlling tumor growth. Curcumin (CUR), an herbal compound with anti-cancer properties, inhibits the efflux of exogenous Ca²⁺ while promoting its excretion from the endoplasmic reticulum into the cytoplasm. To harness these therapeutic modalities, we have developed a nanoplatform that incorporates hollow CuS nanoparticles (NPs) adorned with multiple CaCO₃ particles and internally loaded with CUR. This nanocomposite exhibits high uptake and easy escape from lysosomes, along with the degradation of surrounding CaCO₃, provoking the generation of abundant exogenous Ca²⁺ in situ, ultimately damaging the mitochondria of diseased cells. Impressively, under laser excitation, the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO₃, synergistically enhancing the antitumor effect through photothermal therapy. Additionally, fluorescence imaging reveals the distribution of these nanovehicles in vivo, indicating their effective accumulation at the tumor site. This nanoplatform shows promising outcomes for tumor-targeting and the effective treatment in a murine model of cervical cancer, achieved through cascade enhancement of calcium overload-based dual therapy.