In 2021,approximately 537 million people suffered from diabetes mellitus(DM)globally,and this figure will increase to approximately 783 million within the next quarter-century.The increasing burden of DM is a pressing...In 2021,approximately 537 million people suffered from diabetes mellitus(DM)globally,and this figure will increase to approximately 783 million within the next quarter-century.The increasing burden of DM is a pressing global public health issue.Therefore,the early identification of high-risk groups and implementation of effective intervention measures is imperative.展开更多
Objective： To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell （DC）-T cell therapy on lung cancer. Methods： Transplanted Lewis lung cancer （LLC） models of C57BL/6 ...Objective： To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell （DC）-T cell therapy on lung cancer. Methods： Transplanted Lewis lung cancer （LLC） models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC- T＋endostatin group, DC-T group, and phosphate-buffered saline （PBS） control group. Microvessel density （MVD） of tumor tissue in tumor-bearing mice was determined by immunohistochemistry （IHC）. The expressions of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor-1α （HIF-1α） were determined by Western blotting and IHC staining. The proportions of CD8＋ T cells, mature dendritic cells （mDC）, tumor-associated macrophages [TAM （M1/M2）], and myeloid-derived suppressor cells （MDSC） in suspended cells of tumor tissue were determined by flow cytometry. The expressions of inter｜eukin （IL）-6, IL-10, IL-17, transforming growth factor-β（TGF-β） and interferon-γ （IFN-γ） in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay （ELISA）. Results： DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC- T＋endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ, and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC- T＋endostatin group, the proportions of MDSC and TAM （M2 type） were significantly decreased, mDC and TAM （Nil type） were up-regulated, and CD8＋ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-β and IL-17 in tumor tissue, and enhanced the expression of IFN-γ. Conclusions： The study indicated the synergic antitumor effects between endostatin and tumor antigen-pulsed DC-T cells, which may be a prospective therapy strategy to achieve potent antitumor effects on lung cancer.展开更多
Mitochondrial metabolism plays a pivotal role in tumor progression,yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control.Herein,we present Jahn-Teller...Mitochondrial metabolism plays a pivotal role in tumor progression,yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control.Herein,we present Jahn-Teller distortion-engineered,self-propelled nanorobots(IDP@Z@AP)that integrate catalytic oxygen generation,mitochondria-targeted drug delivery,and real-time 3D NIR-Ⅱ photoacoustic(PA)imaging for precision tumor therapy.The nanorobots are fabricated by co-encapsulating a NIR-Ⅱ photothermal agent(IR1048)and a mitochondria-targeting chemotherapeutic(DOX-TPP)within a ZIF-8 framework,followed by in situ anchoring of ultrasmall AuPt bimetallic nanozymes.Pt-induced Jahn-Teller distortion modulates the electronic structure of AuPt,enhancing glucose oxidase-and catalase-like activities.Under NIR-Ⅱ laser irradiation,photothermalenhanced cascade catalysis drives autonomous motion and catalyzes intratumoral O2 generation,facilitating deep tumor infiltration.In vitro studies reveal efficient mitochondrial targeting,resulting in significant mito-chondrial membrane depolarization,intracellular ATP depletion,and suppressed cell migration and invasion.In vivo,3D NIR-Ⅱ PA imaging enables noninvasive visualization of nanorobot biodistribution and real-time mapping of catalytic oxygen generation within tumor tissues.This nanorobotic platform effectively modulates tumor hypoxia and enhances chemotherapeutic delivery to mitochondria,ultimately achieving potent tumor suppres-sion.The work offers a smart,catalytically driven,mitochondria-targeted strategy with real-time therapeutic feedback for subcellular-level cancer therapy.展开更多
基金supported by the Research Funds of the Center for Big Data and Population Health of IHM(grant number JKS2022015)the Key Scientific Research Fund of the Anhui Provincial Education Department(grant number2023AH050610)the Anhui Natural Science Foundation(grant number 1808085QH252)。
文摘In 2021,approximately 537 million people suffered from diabetes mellitus(DM)globally,and this figure will increase to approximately 783 million within the next quarter-century.The increasing burden of DM is a pressing global public health issue.Therefore,the early identification of high-risk groups and implementation of effective intervention measures is imperative.
基金supported by Natural Science Foundation of Shandong province,China(No.ZR2010HL015)Natural Science Youth Foundation of Shandong province,China(No.ZR2013HQ017)
文摘Objective： To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell （DC）-T cell therapy on lung cancer. Methods： Transplanted Lewis lung cancer （LLC） models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC- T＋endostatin group, DC-T group, and phosphate-buffered saline （PBS） control group. Microvessel density （MVD） of tumor tissue in tumor-bearing mice was determined by immunohistochemistry （IHC）. The expressions of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor-1α （HIF-1α） were determined by Western blotting and IHC staining. The proportions of CD8＋ T cells, mature dendritic cells （mDC）, tumor-associated macrophages [TAM （M1/M2）], and myeloid-derived suppressor cells （MDSC） in suspended cells of tumor tissue were determined by flow cytometry. The expressions of inter｜eukin （IL）-6, IL-10, IL-17, transforming growth factor-β（TGF-β） and interferon-γ （IFN-γ） in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay （ELISA）. Results： DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC- T＋endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ, and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC- T＋endostatin group, the proportions of MDSC and TAM （M2 type） were significantly decreased, mDC and TAM （Nil type） were up-regulated, and CD8＋ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-β and IL-17 in tumor tissue, and enhanced the expression of IFN-γ. Conclusions： The study indicated the synergic antitumor effects between endostatin and tumor antigen-pulsed DC-T cells, which may be a prospective therapy strategy to achieve potent antitumor effects on lung cancer.
基金financially supported by the National Natural Science Foundation of China Regional Innovation and Development Joint Fund(Sichuan)(NSFC,No.U21A20417)the 135 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD24003 and ZYGD23023)the Opening Project of Medical Imaging Key Laboratory of Sichuan Province,North Sichuan Medical College(MIKL202403)。
文摘Mitochondrial metabolism plays a pivotal role in tumor progression,yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control.Herein,we present Jahn-Teller distortion-engineered,self-propelled nanorobots(IDP@Z@AP)that integrate catalytic oxygen generation,mitochondria-targeted drug delivery,and real-time 3D NIR-Ⅱ photoacoustic(PA)imaging for precision tumor therapy.The nanorobots are fabricated by co-encapsulating a NIR-Ⅱ photothermal agent(IR1048)and a mitochondria-targeting chemotherapeutic(DOX-TPP)within a ZIF-8 framework,followed by in situ anchoring of ultrasmall AuPt bimetallic nanozymes.Pt-induced Jahn-Teller distortion modulates the electronic structure of AuPt,enhancing glucose oxidase-and catalase-like activities.Under NIR-Ⅱ laser irradiation,photothermalenhanced cascade catalysis drives autonomous motion and catalyzes intratumoral O2 generation,facilitating deep tumor infiltration.In vitro studies reveal efficient mitochondrial targeting,resulting in significant mito-chondrial membrane depolarization,intracellular ATP depletion,and suppressed cell migration and invasion.In vivo,3D NIR-Ⅱ PA imaging enables noninvasive visualization of nanorobot biodistribution and real-time mapping of catalytic oxygen generation within tumor tissues.This nanorobotic platform effectively modulates tumor hypoxia and enhances chemotherapeutic delivery to mitochondria,ultimately achieving potent tumor suppres-sion.The work offers a smart,catalytically driven,mitochondria-targeted strategy with real-time therapeutic feedback for subcellular-level cancer therapy.
