Hypoxia is a typical characteristic of hepatocellular carcinoma(HCC), which causes tremendous obstacles to tumor treatments. Current first-line treatment may further deteriorate tumor hypoxia. For example,Lenvatinib, ...Hypoxia is a typical characteristic of hepatocellular carcinoma(HCC), which causes tremendous obstacles to tumor treatments. Current first-line treatment may further deteriorate tumor hypoxia. For example,Lenvatinib, a receptor tyrosine kinase inhibitor(RTKI), suppresses tumor growth via blocking vascular endothelial growth factor(VEGF) signaling, and can also inhibit angiogenesis, thus limiting oxygen supply to tumor sites. Therefore, alleviating tumor microenvironment(TME) hypoxia holds great potential for enhancing the therapeutic effect of RTKI. Here, nanoparticle-stabilized oxygen microcapsules, a stable and biocompatible oxygen-loaded delivery system, are successfully prepared through interfacial polymerization of polydopamine nanoparticles. The microcapsules with a large loading capacity of oxygen in the core show excellent bioavailability and dispersity, which could effectively improve the hypoxic TME when they serve as oxygen delivery vehicles. Synergetic treatments of Lenvatinib and oxygen microcapsules could induce the transition of “cold tumor” in an immune-suppressed state to “hot tumor” in an immune-activated state by improving tumor hypoxic TME and reducing angiogenesis in HCC. It is revealed that combined treatments of oxygen microcapsules and Lenvatinib could polarize tumor-associated macrophages(TAMs) to anti-tumor M1 cells and activate T cell-mediated anti-tumor immune responses.The results suggest that synergetic therapy using oxygen microcapsules and Lenvatinib could alleviate the hypoxic TME and enhance the therapeutic performance of RTKI, demonstrating a promising anti-tumor strategy for enhanced therapy of HCC.展开更多
Diphenylarsinic acid(DPAA)is both the prime starting material and major metabolite of chemical weapons(CWs).Because of its toxicity and the widespread distribution of abandoned CWs in burial site,DPAA sorption by natu...Diphenylarsinic acid(DPAA)is both the prime starting material and major metabolite of chemical weapons(CWs).Because of its toxicity and the widespread distribution of abandoned CWs in burial site,DPAA sorption by natural Fe minerals is of considerable interest.Here we report the first study on DPAA sorption by natural magnetite and siderite using macroscopic sorption kinetics,sequential extraction procedure(SEP)and microscopic extended X-ray absorption fine-structure spectroscopy(EXAFS).Our results show that the sorption pseudo-equilibrated in 60 minutes and that close to 50%and 20%–30%removal can be achieved for magnetite and siderite,respectively,at the initial DPAA concentrations of 4–100 mg/L.DPAA sorption followed pseudo-secondary and intra-particle diffusion kinetics models,and the whole process was mainly governed by intra-particle diffusion and chemical bonding.SEP and EXAFS results revealed that DPAA mainly formed inner-sphere complexes on magnetite(>80%),while on siderite it simultaneously resulted in outer-sphere and inner-sphere complexes.EXAFS analysis further confirmed the formation of inner-sphere bidentate binuclear corner-sharing complexes(^(2)C)for DPAA.Comparison of these results with previous studies suggests that phenyl groups are likely to impact the sorption capacity and structure of DPAA by increasing steric hindrance or affecting the way the central arsenic(As)atom maintains charge balance.These results improve our knowledge of DPAA interactions with Fe minerals,which will help to develop remediation technology and predict the fate of DPAA in soil-water environments.展开更多
基金supported by the National Key Research and Development Program of China (Nos. 2019YFA0803000,2019YFC1316000)the National Natural Science Foundation of China (Nos. U20A20378, 21878258)+1 种基金Zhejiang Provincial Natural Science Foundation of China (No. Y20B060027)Scientific Research Fund of Zhejiang Provincial Education Department (No.Y202045652)。
文摘Hypoxia is a typical characteristic of hepatocellular carcinoma(HCC), which causes tremendous obstacles to tumor treatments. Current first-line treatment may further deteriorate tumor hypoxia. For example,Lenvatinib, a receptor tyrosine kinase inhibitor(RTKI), suppresses tumor growth via blocking vascular endothelial growth factor(VEGF) signaling, and can also inhibit angiogenesis, thus limiting oxygen supply to tumor sites. Therefore, alleviating tumor microenvironment(TME) hypoxia holds great potential for enhancing the therapeutic effect of RTKI. Here, nanoparticle-stabilized oxygen microcapsules, a stable and biocompatible oxygen-loaded delivery system, are successfully prepared through interfacial polymerization of polydopamine nanoparticles. The microcapsules with a large loading capacity of oxygen in the core show excellent bioavailability and dispersity, which could effectively improve the hypoxic TME when they serve as oxygen delivery vehicles. Synergetic treatments of Lenvatinib and oxygen microcapsules could induce the transition of “cold tumor” in an immune-suppressed state to “hot tumor” in an immune-activated state by improving tumor hypoxic TME and reducing angiogenesis in HCC. It is revealed that combined treatments of oxygen microcapsules and Lenvatinib could polarize tumor-associated macrophages(TAMs) to anti-tumor M1 cells and activate T cell-mediated anti-tumor immune responses.The results suggest that synergetic therapy using oxygen microcapsules and Lenvatinib could alleviate the hypoxic TME and enhance the therapeutic performance of RTKI, demonstrating a promising anti-tumor strategy for enhanced therapy of HCC.
基金support of the National Natural Science Foundation of China(Nos.41807117,41230858)the Cultivation Project on Excellent Undergraduates’Thesis(design,create)of Anhui Normal University(No.pyjh2020439)the Project of Innovation and Entrepreneurship Training for College Students(No.202110370060).
文摘Diphenylarsinic acid(DPAA)is both the prime starting material and major metabolite of chemical weapons(CWs).Because of its toxicity and the widespread distribution of abandoned CWs in burial site,DPAA sorption by natural Fe minerals is of considerable interest.Here we report the first study on DPAA sorption by natural magnetite and siderite using macroscopic sorption kinetics,sequential extraction procedure(SEP)and microscopic extended X-ray absorption fine-structure spectroscopy(EXAFS).Our results show that the sorption pseudo-equilibrated in 60 minutes and that close to 50%and 20%–30%removal can be achieved for magnetite and siderite,respectively,at the initial DPAA concentrations of 4–100 mg/L.DPAA sorption followed pseudo-secondary and intra-particle diffusion kinetics models,and the whole process was mainly governed by intra-particle diffusion and chemical bonding.SEP and EXAFS results revealed that DPAA mainly formed inner-sphere complexes on magnetite(>80%),while on siderite it simultaneously resulted in outer-sphere and inner-sphere complexes.EXAFS analysis further confirmed the formation of inner-sphere bidentate binuclear corner-sharing complexes(^(2)C)for DPAA.Comparison of these results with previous studies suggests that phenyl groups are likely to impact the sorption capacity and structure of DPAA by increasing steric hindrance or affecting the way the central arsenic(As)atom maintains charge balance.These results improve our knowledge of DPAA interactions with Fe minerals,which will help to develop remediation technology and predict the fate of DPAA in soil-water environments.
