In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in prevalence.The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in...In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in prevalence.The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in the mid-brain with dopaminergic neurons losing.Typical therapeutic solutions,including drugs,deep brain stimulation,and cell transplantation,can only alleviate the symptoms of Parkinson’s disease.It is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic neurons.Herein,we develop a core-satellite-like nanoassembly(PDA-AFn(by integrating polydopamine nanoparticles and apoferritin))to raise the expression of tyrosine hydroxylase(TH),a rate-limiting enzyme in the formation of the dopamine.Both components in the nanoassembly could cooperate with each other,not only elaborately regulate the iron homeostasis and redox microenvironment,but also utilize excessive reactive oxygen species(ROS)and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity,and consequently restore the function of the degenerated neurons.Remarkably,the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model mice.It is an explicit yet inspiring advance in treatment of the neurodegeneration.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
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
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
Glioblastoma multiforme is the most common and lethal brain tumour-type.The current standard of care includes Temozolomide(TMZ)chemotherapy.However,inherent and acquired resistance to TMZ thwart successful treatment.T...Glioblastoma multiforme is the most common and lethal brain tumour-type.The current standard of care includes Temozolomide(TMZ)chemotherapy.However,inherent and acquired resistance to TMZ thwart successful treatment.The direct repair protein methylguanine DNA methyltransferase(MGMT)removes the cytotoxic O6-methylguanine(O6-MeG)lesion delivered by TMZ and so its expression by tumours confers TMZ-resistance.DNA mismatch repair(MMR)is essential to process O6-MeG adducts and MMR-deficiency leads to tolerance of lesions,resistance to TMZ and further DNA mutations.In this article,two strategies to overcome TMZ resistance are discussed:(1)synthesis of imidazotetrazine analogues-designed to retain activity in the presence of MGMT or loss of MMR;(2)preparation of imidazotetrazine-nanoparticles to deliver TMZ preferably to the brain and tumour site.Our promising results encourage belief in a future where better prognoses exist for patients diagnosed with this devastating disease.展开更多
基金This work was supported by National Natural Science Foundation of China(Nos.22175085 and 21875101)National Key Research and Development Program of China(No.2017YFA0701301)State Key Laboratory of Analytical Chemistry for Life Science(No.SKLACLS2219).
文摘In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in prevalence.The main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in the mid-brain with dopaminergic neurons losing.Typical therapeutic solutions,including drugs,deep brain stimulation,and cell transplantation,can only alleviate the symptoms of Parkinson’s disease.It is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic neurons.Herein,we develop a core-satellite-like nanoassembly(PDA-AFn(by integrating polydopamine nanoparticles and apoferritin))to raise the expression of tyrosine hydroxylase(TH),a rate-limiting enzyme in the formation of the dopamine.Both components in the nanoassembly could cooperate with each other,not only elaborately regulate the iron homeostasis and redox microenvironment,but also utilize excessive reactive oxygen species(ROS)and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity,and consequently restore the function of the degenerated neurons.Remarkably,the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model mice.It is an explicit yet inspiring advance in treatment of the neurodegeneration.
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.
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.
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This studentship is supported by the Engineering and Physical Sciences Research Council(EP/L01646X).
文摘Glioblastoma multiforme is the most common and lethal brain tumour-type.The current standard of care includes Temozolomide(TMZ)chemotherapy.However,inherent and acquired resistance to TMZ thwart successful treatment.The direct repair protein methylguanine DNA methyltransferase(MGMT)removes the cytotoxic O6-methylguanine(O6-MeG)lesion delivered by TMZ and so its expression by tumours confers TMZ-resistance.DNA mismatch repair(MMR)is essential to process O6-MeG adducts and MMR-deficiency leads to tolerance of lesions,resistance to TMZ and further DNA mutations.In this article,two strategies to overcome TMZ resistance are discussed:(1)synthesis of imidazotetrazine analogues-designed to retain activity in the presence of MGMT or loss of MMR;(2)preparation of imidazotetrazine-nanoparticles to deliver TMZ preferably to the brain and tumour site.Our promising results encourage belief in a future where better prognoses exist for patients diagnosed with this devastating disease.
