Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is s...Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.展开更多
Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and considerable biocompatibi...Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and considerable biocompatibility. In this work, we fabricate an interesting type of MSNs which are intrinsically doped with photosensitizing molecules, chlorin e6 （Ce6）. By increasing the amount of Ce6 doped inside the silica matrix, it is found that the morphology of MSNs changes from spheres to rod-like shapes. The obtained Ce6-doped mesoporous silica nanorods （CMSNRs） are not only able to produce singlet oxygen for photodynamic therapy, but can also serve as a drug delivery platform with high drug loading capacity by utilizing their mesoporous structure. Compared to spherical nano- particles, it is found that CMSNRs with a larger aspect ratio show much faster uptake by cancer cells. With doxorubicin （DOX） employed as a model drug, the combined photodynamic and chemotherapy is carried out, achieving synergistic anti-tumor effects both in vitro and in vivo. Our study presents a new design of an MSN-based drug delivery platform, which intrinsically is fluorescent and able to serve as a photodynamic agent, promising for future imaging-guided combination therapy of cancer.展开更多
Combination therapy is a promising cancer treatment strategy that is usually based on the utilization of complicated nanostructures with multiple components functioning as photo-thermal energy transducers, photo-sensi...Combination therapy is a promising cancer treatment strategy that is usually based on the utilization of complicated nanostructures with multiple components functioning as photo-thermal energy transducers, photo-sensitizers, or dose intensifiers for phototherma! therapy （PTT）, photodynamic therapy （PDT）, or radiation therapy （RT）. In this study, ultrathin tungsten oxide nanowires （W18O49） were synthesized using a solvothermal approach and examined as a multifunctional theranostic nanoplatform. In vitro and in vivo analyses demonstrated that these nanowires could induce extensive heat- and singlet oxygen-mediated damage to cancer cells under 980 nm near infrared （NIR）-laser excitation. They were also shown to function as radiation dose intensifying agents that enhance irradiative energy deposition locally and selectively during radiation therapy. Compared to NIR-induced PTT/PDT and RT alone, W18O49 - based synergistic tri-modal therapy eradicated xenograft tumors and no recurrence was observed within a 9-month follow up. Moreover, the strong X-ray attenuation ability of the tungsten element （Z = 74, 4.438 cm^2·g^-1, 100 KeV） qualified these nanowires as excellent contrast agents in X-ray-based imaging, such as diagnostic computed tomography （CT） and cone-beam CT for image-guided radiation therapy. Toxicity studies demonstrated minimal adverse effects on the hematologic system and major organs of mice within one month. In conclusion, these nanowires have shown significant potential for cancer therapy with inherent image guidance and synergistic effects from phototherapy and radiation therapy, which warrants further investigation.展开更多
基金financially supported by the National Natural Science Foundation of China (21807073, 31771036 and 51703132)the Basic Research Program of Shenzhen (JCYJ20170818144745087, JCYJ20180507182413022 and JCYJ20170412111100742)+2 种基金Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003)Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)China Postdoctoral Science Foundation (2018M630987 and 2019T120752)
文摘Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.
基金This work was partially supported by the National Basic Research Programs of China （973 Program） （Nos. 2012CB932600 and 2011CB911002）, the National Natural Science Foundation of China （Nos. 51222203 and 51132006）, Jiangsu Key Laboratory for Carbon- Based Functional Materials and Devices, a Jiangsu Natural Science Fund for Distinguished Young Scholars, and a Project Funded by the Priority Academic Program Development （PAPD） of Jiangsu Higher Education Institutions.
文摘Mesoporous silica nanoparticles （MSNs） have attracted tremendous attention in recent years as drug delivery carriers due to their large surface areas, tunable sizes, facile modification and considerable biocompatibility. In this work, we fabricate an interesting type of MSNs which are intrinsically doped with photosensitizing molecules, chlorin e6 （Ce6）. By increasing the amount of Ce6 doped inside the silica matrix, it is found that the morphology of MSNs changes from spheres to rod-like shapes. The obtained Ce6-doped mesoporous silica nanorods （CMSNRs） are not only able to produce singlet oxygen for photodynamic therapy, but can also serve as a drug delivery platform with high drug loading capacity by utilizing their mesoporous structure. Compared to spherical nano- particles, it is found that CMSNRs with a larger aspect ratio show much faster uptake by cancer cells. With doxorubicin （DOX） employed as a model drug, the combined photodynamic and chemotherapy is carried out, achieving synergistic anti-tumor effects both in vitro and in vivo. Our study presents a new design of an MSN-based drug delivery platform, which intrinsically is fluorescent and able to serve as a photodynamic agent, promising for future imaging-guided combination therapy of cancer.
基金Acknowledgements This work has been financially supported by the National Natural Science Foundation of China （Nos. 51372260, 51132009, and 21172043）, the Shanghai Rising-Star Program （No. 12QH1402500）, the Science and Technology Commission of Shanghai （No. 11nm0505000 and 124119a0400）, the Shanghai Municipal Commission of Health （No. 20134360）, the Development Foundation for Talents of Shanghai （No. 2012035）.
文摘Combination therapy is a promising cancer treatment strategy that is usually based on the utilization of complicated nanostructures with multiple components functioning as photo-thermal energy transducers, photo-sensitizers, or dose intensifiers for phototherma! therapy （PTT）, photodynamic therapy （PDT）, or radiation therapy （RT）. In this study, ultrathin tungsten oxide nanowires （W18O49） were synthesized using a solvothermal approach and examined as a multifunctional theranostic nanoplatform. In vitro and in vivo analyses demonstrated that these nanowires could induce extensive heat- and singlet oxygen-mediated damage to cancer cells under 980 nm near infrared （NIR）-laser excitation. They were also shown to function as radiation dose intensifying agents that enhance irradiative energy deposition locally and selectively during radiation therapy. Compared to NIR-induced PTT/PDT and RT alone, W18O49 - based synergistic tri-modal therapy eradicated xenograft tumors and no recurrence was observed within a 9-month follow up. Moreover, the strong X-ray attenuation ability of the tungsten element （Z = 74, 4.438 cm^2·g^-1, 100 KeV） qualified these nanowires as excellent contrast agents in X-ray-based imaging, such as diagnostic computed tomography （CT） and cone-beam CT for image-guided radiation therapy. Toxicity studies demonstrated minimal adverse effects on the hematologic system and major organs of mice within one month. In conclusion, these nanowires have shown significant potential for cancer therapy with inherent image guidance and synergistic effects from phototherapy and radiation therapy, which warrants further investigation.
