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 m...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.展开更多
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).
文摘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.