Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders,such as Alzheimer’s disease(AD),which can be induced by an excess of reactive oxygen speci...Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders,such as Alzheimer’s disease(AD),which can be induced by an excess of reactive oxygen species(ROS).As an antioxidant,hydrogen gas(H_(2))has the potential to mitigate AD by scavenging highly harmful ROS such as·OH.However,conventional administration methods of H_(2) face significant challenges in controlling H_(2) release on demand and fail to achieve effective accumulation at lesion sites.Herein,we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared(NIR)light-driven photocatalytic H_(2) evolution in situ.The nanoreactors are constructed by biocompatible crosslinked vesicles(CVs)encapsulating ascorbic acid and two photosensitizers,chlorophyll a(Chla)and indoline dye(Ind).In addition,platinum nanoparticles(Pt NPs)serve as photocatalysts and upconversion nanoparticles(UCNP)act as light-harvesting antennas in the nanoreacting system,and both attach to the surface of CVs.Under NIR irradiation,the nanoreactors release H_(2) in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model.Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.展开更多
基金supported by the Shenzhen Science and Technology Program-Basic Research Scheme(JCYJ20220531090808020)the Research Grants Council(RGC)of Hong Kong Collaborative Research Grant(C5005-23W and C5078-21E)+7 种基金the Research Grants Council(RGC)of Hong Kong General Research Grant(PolyU 15217621 and PolyU 15216622)the Guangdong-Hong Kong Technology Cooperation Funding Scheme(GHP/032/20SZ and SGDX20201103095404018)the Hong Kong Polytechnic University Shenzhen Institute Bai Cheng Bai Yuan Fund(I2022A002)PolyU Internal Fund(1-YWB4,1-WZ4E,1-CD8M,1-WZ4E,1-CEB1,1-YWDU,1-CE2J and 1-W02C)the funding from the Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center(No.:LMDBCXRC202401 and LMDBCXRC202402)Shandong Provincial Overseas Excellent Young Scholar Program(2024HWYQ-042 and 2024HWYQ-043)Taishan Scholar Youth Expert Program of Shandong Province(tsqn202306102 and tsqn202312105)supporting this worksupported by the University Research Facility in Life Sciences of the Hong Kong Polytechnic University.
文摘Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders,such as Alzheimer’s disease(AD),which can be induced by an excess of reactive oxygen species(ROS).As an antioxidant,hydrogen gas(H_(2))has the potential to mitigate AD by scavenging highly harmful ROS such as·OH.However,conventional administration methods of H_(2) face significant challenges in controlling H_(2) release on demand and fail to achieve effective accumulation at lesion sites.Herein,we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared(NIR)light-driven photocatalytic H_(2) evolution in situ.The nanoreactors are constructed by biocompatible crosslinked vesicles(CVs)encapsulating ascorbic acid and two photosensitizers,chlorophyll a(Chla)and indoline dye(Ind).In addition,platinum nanoparticles(Pt NPs)serve as photocatalysts and upconversion nanoparticles(UCNP)act as light-harvesting antennas in the nanoreacting system,and both attach to the surface of CVs.Under NIR irradiation,the nanoreactors release H_(2) in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model.Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.
