CaCO_(3)-encircled hollow CuS nanovehicles to suppress cervical cancer through enhanced calcium overload-triggered mitochondria damage  

作　　者：Pengfei Wang Xichen Sun Liuyan Tang Ningning Li Qing Wang Bicheng Gan Yuezhou Zhang 

机构地区：[1]Xi’an Institute of Flexible Electronics(IFE)and Xi’an Institute of Biomedical Materials&Engineering(IBME),Northwestern Polytechnical University,Xi’an 710072,China [2]Ningbo Institute of Northwestern Polytechnical University,Frontiers Science Center for Flexible Electronics(FSCFE),Key laboratory of Flexible Electronics of Zhejiang Province,Ningbo 315103,China [3]College of Petroleum Engineering,Heilongjiang,Northeast Petroleum University,Daqing 163318,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第6期138-153,共16页亚洲药物制剂科学（英文）

基　　金：This research was sponsored by the key research program of Ningbo(No.2023Z210);funded by Ningbo Natural Science Foundation(No.202003N4006);the Joint Research Funds of Department of Science&Technology of Shaanxi Province,Northwestern Polytechnical University(No.2020GXLH-Z-017).

摘　　要：Cervical cancer stands is a formidablemalignancy that poses a significant threat towomen’s health.Calcium overload,a minimally invasive tumor treatment,aims to accumulate an excessive concentration of Ca^(2+)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^(2+)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_(3) 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 Ca^(2+)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 CaCO_(3),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.

关 键 词：Hollow CuS nanovehicles Tumor-specific synergistic therapy Mitochondrial damage Cascade-enhanced calcium overload 

分 类 号：R737.33[医药卫生—肿瘤]