摘要
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.
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)
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 work
supported by the University Research Facility in Life Sciences of the Hong Kong Polytechnic University.
