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

• Published in: Asian journal of pharmceutical sciences 2024-12, Vol.19 (6), p.100989, Article 100989
• Main Authors: Wang, Pengfei, Sun, Xichen, Tang, Liuyan, Li, Ningning, Wang, Qing, Gan, Bicheng, Zhang, Yuezhou
• Format: Article
• Language: English
• Subjects: Cascade-enhanced calcium overload; Hollow CuS nanovehicles; Mitochondrial damage; Tumor-specific synergistic therapy
• ISSN: 1818-0876; 2221-285X; 2221-285X
• DOI: 10.1016/j.ajps.2024.100989

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. The bionic raspberry-shaped nano drug delivery system was loaded with curcumin (CUR). When injected into tumor-bearing mice through the tail vein, a large amount of exogenous Ca2+ were generated in the cancer cells in situ. The synergistic effect of CUR causes intracellular calcium overload, leading to a decrease in mitochondrial membrane potential (MMP) and ATP production levels. The photothermal effect produced by CuS under laser excitation promoted the degradation of CaCO3, and acted synergistically on the tumor in the form of photothermal therapy. [Display omitted]