To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex bas...To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex based on apoferritin(AFt).To this end,we rationally designed and synthesized a trinuclear Gd(Ⅲ)complex(Gd3)with strong T_(1)-weighted MRI performance and remarkable cytotoxicity against glioma cells in vitro.Subsequently,we constructed an AFt-Gd3 nanoparticle(NP)delivery system.AFt-Gd3 NPs not only penetrate BBB but also provide significant T_(1)-weighted MRI contrast for orthotopic glioma while effectively inhibiting glioma growth with minimal side effects in vivo.Furthermore,we elucidate the mechanism by which AFt-Gd3 NPs inhibit glioma growth:inducing apoptosis through chemodynamic therapy,blocking glutamine metabolism,and inhibiting energy metabolism.展开更多
Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy.In the present work,an apoferritin(AFt)nanoparticle wa...Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy.In the present work,an apoferritin(AFt)nanoparticle was tested as influenza vaccine carrier by chemically conjugating a matrix protein 2 ectodomain(M2e)antigen peptide or/and the full-length hemagglutinin(HA)antigen on the outer surface of the AFt,with heterobifunctional sSMCC or SM(PEG)_(24) containing PEG chain as linkers.To each AFt nanoparticle,about 30-32 M2e or 1.8 HA antigen could be coupled.The AFt-(PEG)24-M2e,in which the M2e was coupled through SM(PEG)_(24) containing PEG chain,conferred higher protective efficacy in immunized mice than AFt-M2e did,but was less effective than AFt-(PEG)_(24)-HA.When both M2e and HA were coupled,the synthesized dual-antigen vaccine candidate AFt-(PEG)_(24)-M2e/HA elicited high level of M2e and HA antigen-specific antibodies and conferred 100%protection against lethal infection of homologous PR8 HI N1 virus strain and 70%protection against a heterologous A/FM/1/47(FM1,H1N1)strain,which was more effective than the M2e or HA single antigen vaccine candidates.The potential cross-protective effect of the dual-antigen vaccine was further demonstrated by significant specific hemagglutination inhibition(HAI)titers in serum of the immunized mice against three other heterologous viral strains including A/Singapore/GPl908/2015(IVR-180)H1N1,A/Anhui/1/2005 H5N1,and A/Hong Kong H3N2.展开更多
Alcohol abuse induced liver damage are closely related to oxidative stress,several efforts have been made to quench free radicals produced in the liver.Heteropolymeric soybean seed ferritin has been proved to protect ...Alcohol abuse induced liver damage are closely related to oxidative stress,several efforts have been made to quench free radicals produced in the liver.Heteropolymeric soybean seed ferritin has been proved to protect DNA from oxidative damage.However,the roles of homopolymeric apoferritin in quenching free radicals have been neglected so far.In order to improve the ferroxidase activity of ferritin,we have prepared apo ferritin by removing iron core from the cavity.In this study,the roles of apo shrimp ferritin(Marsupenaeus japonicus ferritin,MjFer)and human H chain ferritin(HuHF)in attenuating the hydroxyl radicals in vitro and in vivo has been investigated.Results showed that MjFer was able to quench the free radicals produced by iron oxidation more efficiently than HuHF in vitro.Animal studies using a mouse model of alcohol-induced acute liver injury revealed that MjFer is much more efficacious than HuHF in alleviating the liver injury,by attenuating oxidative stress and regulating Nrf2/HO1 expression.Accordingly,the higher activity of MjFer may be attributed to its faster iron oxidative rate than HuHF,which may help improve the intestinal integrity,and reduce abnormal iron absorption.As expected,iron contents in the liver of MjFer and HuHF group are much lower than that of model group,further alleviating the liver damage.These findings suggest that apoferritin may be a promising candidate for alcohol-induced liver injury.展开更多
Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of whic...Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of which remains largely undefined. Here I report the biochemical purification of iron-loaded ferritin as an active ingredient of fly extract that is required for promoting the growth of clone 8 imaginal disc cells. Consistent with an essential role for iron- loaded ferritin in cultured cells, overexpression of ferritin or addition of iron in a nutrient-poor diet increases animal viability and body weight, promotes cell proliferation, and shortens the duration of postembryonic development. Conversely, overexpression of dominant-negative ferritin or addition of iron chelator causes the opposite effects. Fer- ritin mutant flies arrest development at the first-instar larval stage with a severe starvation phenotype reminiscent of that seen in starved larvae. I conclude that iron-loaded ferritin acts as an essential mitogen for cell proliferation and postembryonic development in Drosophila by maintaining iron homeostasis and antagonizing starvation response.展开更多
OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character ...OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.展开更多
基金supported by the Natural Science Foundation of Guangxi(2022GXNSFGA035003)Natural Science Foundation of China(82404419,22077021)the Guangxi"Bagui"Scholar Program to F.Y.
文摘To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex based on apoferritin(AFt).To this end,we rationally designed and synthesized a trinuclear Gd(Ⅲ)complex(Gd3)with strong T_(1)-weighted MRI performance and remarkable cytotoxicity against glioma cells in vitro.Subsequently,we constructed an AFt-Gd3 nanoparticle(NP)delivery system.AFt-Gd3 NPs not only penetrate BBB but also provide significant T_(1)-weighted MRI contrast for orthotopic glioma while effectively inhibiting glioma growth with minimal side effects in vivo.Furthermore,we elucidate the mechanism by which AFt-Gd3 NPs inhibit glioma growth:inducing apoptosis through chemodynamic therapy,blocking glutamine metabolism,and inhibiting energy metabolism.
基金supported by the National Natural Science Foundation of China(Nos.21821005,31970872).
文摘Ferritin nanoparticles with self-assembling properties have been widely explored as vaccine carrier by displaying foreign antigens through genetic fusion strategy.In the present work,an apoferritin(AFt)nanoparticle was tested as influenza vaccine carrier by chemically conjugating a matrix protein 2 ectodomain(M2e)antigen peptide or/and the full-length hemagglutinin(HA)antigen on the outer surface of the AFt,with heterobifunctional sSMCC or SM(PEG)_(24) containing PEG chain as linkers.To each AFt nanoparticle,about 30-32 M2e or 1.8 HA antigen could be coupled.The AFt-(PEG)24-M2e,in which the M2e was coupled through SM(PEG)_(24) containing PEG chain,conferred higher protective efficacy in immunized mice than AFt-M2e did,but was less effective than AFt-(PEG)_(24)-HA.When both M2e and HA were coupled,the synthesized dual-antigen vaccine candidate AFt-(PEG)_(24)-M2e/HA elicited high level of M2e and HA antigen-specific antibodies and conferred 100%protection against lethal infection of homologous PR8 HI N1 virus strain and 70%protection against a heterologous A/FM/1/47(FM1,H1N1)strain,which was more effective than the M2e or HA single antigen vaccine candidates.The potential cross-protective effect of the dual-antigen vaccine was further demonstrated by significant specific hemagglutination inhibition(HAI)titers in serum of the immunized mice against three other heterologous viral strains including A/Singapore/GPl908/2015(IVR-180)H1N1,A/Anhui/1/2005 H5N1,and A/Hong Kong H3N2.
基金supported by the National Key R&D Program of China(2018YFD0901004).
文摘Alcohol abuse induced liver damage are closely related to oxidative stress,several efforts have been made to quench free radicals produced in the liver.Heteropolymeric soybean seed ferritin has been proved to protect DNA from oxidative damage.However,the roles of homopolymeric apoferritin in quenching free radicals have been neglected so far.In order to improve the ferroxidase activity of ferritin,we have prepared apo ferritin by removing iron core from the cavity.In this study,the roles of apo shrimp ferritin(Marsupenaeus japonicus ferritin,MjFer)and human H chain ferritin(HuHF)in attenuating the hydroxyl radicals in vitro and in vivo has been investigated.Results showed that MjFer was able to quench the free radicals produced by iron oxidation more efficiently than HuHF in vitro.Animal studies using a mouse model of alcohol-induced acute liver injury revealed that MjFer is much more efficacious than HuHF in alleviating the liver injury,by attenuating oxidative stress and regulating Nrf2/HO1 expression.Accordingly,the higher activity of MjFer may be attributed to its faster iron oxidative rate than HuHF,which may help improve the intestinal integrity,and reduce abnormal iron absorption.As expected,iron contents in the liver of MjFer and HuHF group are much lower than that of model group,further alleviating the liver damage.These findings suggest that apoferritin may be a promising candidate for alcohol-induced liver injury.
文摘Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of which remains largely undefined. Here I report the biochemical purification of iron-loaded ferritin as an active ingredient of fly extract that is required for promoting the growth of clone 8 imaginal disc cells. Consistent with an essential role for iron- loaded ferritin in cultured cells, overexpression of ferritin or addition of iron in a nutrient-poor diet increases animal viability and body weight, promotes cell proliferation, and shortens the duration of postembryonic development. Conversely, overexpression of dominant-negative ferritin or addition of iron chelator causes the opposite effects. Fer- ritin mutant flies arrest development at the first-instar larval stage with a severe starvation phenotype reminiscent of that seen in starved larvae. I conclude that iron-loaded ferritin acts as an essential mitogen for cell proliferation and postembryonic development in Drosophila by maintaining iron homeostasis and antagonizing starvation response.
基金The project supported by the general grant fund from Hong Kong Research Grant Committee(476912)Health and Medical Research Fund(13120442)Innovation and Technology Fund of Shenzhen(CXZZ20120619150627260)
文摘OBJECTIVE To prepare hypocrellin B-loaded apoferritin nanoparticles(HB-AFT NPs)for photodynamic therapy on tumor.METHODS HB-AFT NPs were prepared by taking advantage of the reversibleunfolding and refolding character of apoferritin in different pH environments.The photophysical and photobiological properties of hypocrellin B-loaded apoferritin were measured.RESULETS HB molecules were successfully encapsulated within apoferritincavity.HB-AFT-NPs exhibited higher ROS productionthan free HB.Additionally,phototoxicity of HB-AFT NPs to MDA-MB-231 cells was significantly improved as compared to free HB.CONCLUSION Together these results demonstrate that hypocrellin B-loaded apoferritin might be a potential nanoscale photosensitizer.
