Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTH...Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTHCPSi NPs） loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody （Ab） were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi （Un-Ab） NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.展开更多
Multimodal cancer synergistic therapy exhibited remarkable advantages over monotherapy in producing an improved therapeutic efficacy. In this work, Janus-type γ-Fe2 O3/SiO2 nanoparticles(JFSNs) are conjugated with gl...Multimodal cancer synergistic therapy exhibited remarkable advantages over monotherapy in producing an improved therapeutic efficacy. In this work, Janus-type γ-Fe2 O3/SiO2 nanoparticles(JFSNs) are conjugated with glucose oxidase(GOx) for synergistic cancer starvation/chemodynamic therapy. The γ-Fe2O3 hemisphere of JFSNs can perform photoacoustic/T2 magnetic resonance dual-modal imaging of tumors.GOx on the surface of JFSNs catalyzes the decomposition of glucose and produces H2O2 for cancer starvation therapy. Subsequently, the γ-Fe2O3 hemisphere catalyzes the disproportionation of H2O2 to generate highly reactive hydroxyl radicals in an acidic tumor microenvironment. The close distance between GOx and JFSNs ensures adequate contact between the γ-Fe2O3 hemisphere and its substrate H2O2, thus enhancing the catalytic efficiency. This synergy of glucose depletion, biotoxic H2O2 and hydroxyl radicals significantly suppresses 4 T1 mammary tumor growth with minimal adverse effects.展开更多
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
文摘Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTHCPSi NPs） loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody （Ab） were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi （Un-Ab） NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0704003)the Basic Research Program of Shenzhen(JCYJ20180305163452667,JCYJ20180507182413022,and JCYJ20170412111100742)+3 种基金the National Natural Science Foundation of China(81903564,31771036,51703132,and 21874119)the Guangdong Provincial Natural Science Foundation of Major Basic Research and Cultivation Project(2018B030308003)the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China(161032)We thank Instrumental Analysis Center of Shenzhen University(Lihu Campus).
文摘Multimodal cancer synergistic therapy exhibited remarkable advantages over monotherapy in producing an improved therapeutic efficacy. In this work, Janus-type γ-Fe2 O3/SiO2 nanoparticles(JFSNs) are conjugated with glucose oxidase(GOx) for synergistic cancer starvation/chemodynamic therapy. The γ-Fe2O3 hemisphere of JFSNs can perform photoacoustic/T2 magnetic resonance dual-modal imaging of tumors.GOx on the surface of JFSNs catalyzes the decomposition of glucose and produces H2O2 for cancer starvation therapy. Subsequently, the γ-Fe2O3 hemisphere catalyzes the disproportionation of H2O2 to generate highly reactive hydroxyl radicals in an acidic tumor microenvironment. The close distance between GOx and JFSNs ensures adequate contact between the γ-Fe2O3 hemisphere and its substrate H2O2, thus enhancing the catalytic efficiency. This synergy of glucose depletion, biotoxic H2O2 and hydroxyl radicals significantly suppresses 4 T1 mammary tumor growth with minimal adverse effects.
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.
