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碳酸钙包裹的中空硫化铜纳米载体通过增强钙超载引发的线粒体损伤来抑制宫颈癌。

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

作者信息

Wang Pengfei, Sun Xichen, Tang Liuyan, Li Ningning, Wang Qing, Gan Bicheng, Zhang Yuezhou

机构信息

Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering (IBME), Northwestern Polytechnical University, Xi'an 710072, China.

College of Petroleum Engineering, Heilongjiang, Northeast Petroleum University, Daqing 163318, China.

出版信息

Asian J Pharm Sci. 2024 Dec;19(6):100989. doi: 10.1016/j.ajps.2024.100989. Epub 2024 Nov 2.

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 Ca 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 Ca 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 CaCO particles and internally loaded with CUR. This nanocomposite exhibits high uptake and easy escape from lysosomes, along with the degradation of surrounding CaCO, provoking the generation of abundant exogenous Ca , ultimately damaging the mitochondria of diseased cells. Impressively, under laser excitation, the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO, synergistically enhancing the antitumor effect through photothermal therapy. Additionally, fluorescence imaging reveals the distribution of these nanovehicles , 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.

摘要

宫颈癌是一种严重的恶性肿瘤,对女性健康构成重大威胁。钙超载作为一种微创肿瘤治疗方法,旨在使线粒体中积累过量的钙,从而引发细胞凋亡。硫化铜(CuS)是一种用于肿瘤热疗的光热介质。然而,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,它能抑制外源性钙的外流,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,该平台包含中空的CuS纳米颗粒(NPs),这些纳米颗粒装饰有多个碳酸钙颗粒,并内部负载有CUR。这种纳米复合材料具有高摄取率且易于从溶酶体中逃逸,同时周围的碳酸钙会降解,引发大量外源性钙的产生,最终损害病变细胞的线粒体。令人印象深刻的是,在激光激发下,CuS NPs表现出光热效应,加速了碳酸钙的降解,通过光热疗法协同增强了抗肿瘤效果。此外,荧光成像揭示了这些纳米载体的分布,表明它们在肿瘤部位有效积累。通过基于钙超载的双重疗法的级联增强,这种纳米平台在宫颈癌小鼠模型中显示出肿瘤靶向和有效治疗的良好前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd5d/11616050/f7c3b657c5c2/ga1.jpg

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