Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approve...Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.展开更多
Ni-based catalysts are widely investigated non-noble metal-based systems for CO_(2)methanation.However,their industrial application is still limited due to lower activity at low-temperature and catalyst deactivation.I...Ni-based catalysts are widely investigated non-noble metal-based systems for CO_(2)methanation.However,their industrial application is still limited due to lower activity at low-temperature and catalyst deactivation.Incorporating a second metal such as Ru and Fe is considered as a successful strategy to overcome these challenges through alloy formation or the synergies provided by the interplay of two adjacent metallic sites.Nonetheless,their promotional effect on the CO_(2)methanation mechanism under similar conditions has not been reported yet.In this work,Fe and Ru-promoted Ni/ZrO_(2)catalysts were investigated to evaluate their promotional effect on the mechanism.The Ni/Fe ratio was first optimized and a CO_(2)conversion rate of 37.7 mmolCO_(2)/(molNi+Fes)and 96.3%CH^(4)selectivity was obtained over the Ni_(0.8)Fe_(0.2)/ZrO_(2)catalyst.In comparison with Ni_(0.8)Fe_(0.2)/ZrO_(2),Ni_(0.8)Ru_(0.2)/ZrO_(2)prepared with the same composition showed higher activity and stability in CO_(2)methanation.Characterization results indicate alloys formation and H spillover for Ni_(0.8)Ru_(0.2)/ZrO_(2)to be responsible for promotion.Besides,in situ DRIFTS studies evidenced the occurrence of both CO_(2)dissociative and associative pathways over Ni_(0.8)Ru_(0.2)/ZrO_(2)catalyst,while solely the CO_(2)associative pathway occurred for Ni_(0.8)Fe_(0.2)/ZrO_(2)展开更多
Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and en...Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma.By an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization.After G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral core.Importantly,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo.As a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side effects.Remarkably,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake.Moreover,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug release.Encouragingly,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.展开更多
For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs...For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81873196)Sino-German Center for Research Promotion(Project No.:GZ1505)Chinese Scholarship Council,and Science and Technology Planning Projects of Jiaxing City(Project No.:2022AY10014).
文摘Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.
基金supported by JARA-Energy(Seed Fund–JARAENERGY MF 005-17 and the joined project“value chains based on CO_(2)”)the Cluster of Excellence Fuel Science Center(EXC 2186,ID:390919832),which is funded by the Excellence Initiative by the German federal and state governments to promote science and research at German universities+1 种基金supported by the National Key Research and Development Program of China(2019YFA0405602)China Scholarship Council(201806420028)。
文摘Ni-based catalysts are widely investigated non-noble metal-based systems for CO_(2)methanation.However,their industrial application is still limited due to lower activity at low-temperature and catalyst deactivation.Incorporating a second metal such as Ru and Fe is considered as a successful strategy to overcome these challenges through alloy formation or the synergies provided by the interplay of two adjacent metallic sites.Nonetheless,their promotional effect on the CO_(2)methanation mechanism under similar conditions has not been reported yet.In this work,Fe and Ru-promoted Ni/ZrO_(2)catalysts were investigated to evaluate their promotional effect on the mechanism.The Ni/Fe ratio was first optimized and a CO_(2)conversion rate of 37.7 mmolCO_(2)/(molNi+Fes)and 96.3%CH^(4)selectivity was obtained over the Ni_(0.8)Fe_(0.2)/ZrO_(2)catalyst.In comparison with Ni_(0.8)Fe_(0.2)/ZrO_(2),Ni_(0.8)Ru_(0.2)/ZrO_(2)prepared with the same composition showed higher activity and stability in CO_(2)methanation.Characterization results indicate alloys formation and H spillover for Ni_(0.8)Ru_(0.2)/ZrO_(2)to be responsible for promotion.Besides,in situ DRIFTS studies evidenced the occurrence of both CO_(2)dissociative and associative pathways over Ni_(0.8)Ru_(0.2)/ZrO_(2)catalyst,while solely the CO_(2)associative pathway occurred for Ni_(0.8)Fe_(0.2)/ZrO_(2)
基金This research was financially supported by the Sino-German Center for Research Promotion(GZ1505),DFG(SFB 985,Functional Microgels and Microgel Systems),National Natural Science Foundation of China(81801704 and 81761148028)Science and Technology Commission of Shanghai Municipality(18520750400)Shanghai Sailing Program(18YF1415300)。
文摘Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma.By an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization.After G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral core.Importantly,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo.As a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side effects.Remarkably,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake.Moreover,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug release.Encouragingly,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.
基金This research was financially supported by the Sino-German Center for Research Promotion(GZ1505)National Natural Science Foundation of China(81801704 and 81761148028)+5 种基金the Science and Technology Commission of Shanghai Municipality(19XD1400100)Shanghai Sailing Program(18YF1415300)the China Scholarship Council(for X.Li)X.Shi also thanks the support by FCT-Fundaçao para a Ciencia e a Tecnologia through the CQM Base Fund-UIDB/00674/2020Programmatic Fund-UIDP/00674/2020by ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao,through the project M1420-01-0145-FEDER-000005-Centro de Química da Madeira-CQM+(Madeira 14-20 Program).
文摘For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.
