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.

中文翻译：

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CaCO3 环绕的空心 CuS 纳米载体通过增强钙超负荷触发的线粒体损伤抑制宫颈癌


宫颈癌支架是一种可怕的恶性肿瘤，对女性健康构成重大威胁。钙超负荷是一种微创肿瘤治疗方法，旨在在线粒体内积累过量浓度的 Ca2+，从而触发细胞凋亡。硫化铜 （CuS） 是肿瘤热疗的光热介质。然而，仅仅依靠热疗往往不足以控制肿瘤生长。姜黄素 （CUR） 是一种具有抗癌特性的草药化合物，可抑制外源性 Ca2+ 的外排，同时促进其从内质网排泄到细胞质中。为了利用这些治疗方式，我们开发了一种纳米平台，该平台结合了空心 CuS 纳米颗粒 （NP），其中装饰有多个 CaCO3 颗粒，内部加载有 CUR。这种纳米复合材料表现出高摄取和容易从溶酶体中逃逸，以及周围 CaCO3 的降解，引发大量外源性 Ca2+ 原位产生，最终破坏患病细胞的线粒体。令人印象深刻的是，在激光激发下，CuS NPs 表现出光热效应，可加速 CaCO3 的降解，通过光热疗法协同增强抗肿瘤作用。此外，荧光成像揭示了这些纳米载体在体内的分布，表明它们在肿瘤部位的有效积累。该纳米平台通过基于钙超负荷的双重疗法的级联增强实现，在宫颈癌小鼠模型中显示出肿瘤靶向和有效治疗的有希望的结果。