A biomimetic upconversion nanoreactors for near-infrared driven H2 release to inhibit tauopathy in Alzheimer’s disease therapy  

作　　者：Qin Zhang Chuanqi Li Bohan Yin Jiaxiang Yan Yutian Gu Yingying Huang Jiareng Chen Xinyue Lao Jianhua Hao Changqing Yi Yi Zhou James Chung Wai Cheung Siu Hong Dexter Wong Mo Yang 

机构地区：[1]School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaLaboratory for Marine Drugs and [2]Bioproducts,Qingdao Marine Science and Technology Center,Qingdao,266237,China [3]Department of Biomedical Engineering,The Hong Kong Polytechnic University,999077,Hong Kong,China [4]The Hong Kong Polytechnic University Shenzhen Research Institute,Shenzhen,518000,China [5]Research Center for Nanoscience and Nanotechnology,The Hong Kong Polytechnic University,Kowloon,999077,Hong Kong,China [6]Joint Research Center of Biosensing and Precision Theranostics,The Hong Kong Polytechnic University,Kowloon,999077,Hong Kong,China [7]Department of Applied Physics,The Hong Kong Polytechnic University,999077,Hong Kong,China [8]Key Laboratory of Sensing Technology and Biomedical Instruments(Guangdong Province),School of Biomedical Engineering,Sun Yat-Sen University,Guangzhou,510000,China [9]Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China

出　　处：《Bioactive Materials》2024年第12期165-177,共13页生物活性材料（英文）

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.

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.

关 键 词：Artificial photosynthesis Hydrogen therapy Oxidative stress Tau hyperphosphorylation Alzheimer’s disease 

分 类 号：R749.16[医药卫生—神经病学与精神病学]