Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice

Wu, Chengling1,2,3; Xie, Jingyu4,5; Yao, Qingxin1,3; Song, Yilin4,5; Yang, Gucheng4,5; Zhao, Jie3; Zhang, Ruijia1,3; Wang, Ting3; Jiang, Xingyu6; Cai, Xinxia4,5; Gao, Yuan1,3

2024-07-01

10.1002/adma.202314310

ADVANCED MATERIALS   影响因子和分区

0935-9648

1521-4095

["The precise delivery of anti-seizure medications (ASM) to epileptic loci remains the major challenge to treat epilepsy without causing adverse drug reactions. The unprovoked nature of epileptic seizures raises the additional need to release ASMs in a spatiotemporal controlled manner. Targeting the oxidative stress in epileptic lesions, here the reactive oxygen species (ROS) induced in situ supramolecular assemblies that synergized bioorthogonal reactions to deliver inhibitory neurotransmitter (GABA) on-demand, are developed. Tetrazine-bearing assembly precursors undergo oxidation and selectively self-assemble under pathological conditions inside primary neurons and mice brains. Assemblies induce local accumulation of tetrazine in the hippocampus CA3 region, which allows the subsequent bioorthogonal release of inhibitory neurotransmitters. For induced acute seizures, the sustained release of GABA extends the suppression than the direct supply of GABA. In the model of permanent damage of CA3, bioorthogonal ligation on assemblies provides a reservoir of GABA that behaves prompt release upon 365 nm irradiation. Incorporated with the state-of-the-art microelectrode arrays, it is elucidated that the bioorthogonal release of GABA shifts the neuron spike waveforms to suppress seizures at the single-neuron precision. The strategy of in situ supramolecular assemblies-directed bioorthogonal prodrug activation shall be promising for the effective delivery of ASMs to treat epilepsy.","An imbalance between neuronal inhibition and excitation may lead to the onset of epilepsy. In this study, bioorthogonal decaging reactions and photolysis enable on-demand drug release to address the deficiency of an inhibitory neurotransmitter (GABA) during seizure symptoms. Such a spatiotemporal-controlled drug delivery system is applicable for managing epileptic seizures with an unprovoked nature. image"]

bioorthogonal chemistry drug delivery epilepsy microelectrode array self-assembly

SCI ; EI

英语

其他

National Key R&D Program of China[2023YFC2411203] ; Fundamental Research Funds for the Central Universities[buctrc202308] ; null[32122045] ; null[T2293731] ; null[62121003]

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter

WOS:001210963000001

WILEY-V C H VERLAG GMBH

20241816021465

Mammals ; Microelectrodes ; Neurons ; Self assembly ; Supramolecular chemistry ; Targeted drug delivery

Biology:461.9 ; Physical Chemistry:801.4 ; Materials Science:951

MATERIALS SCIENCE

Web of Science

1.Beijing Univ Chem Technol, Coll Mat Sci & Engn, State Key Lab Chem Resource Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
2.Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China
3.Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
4.Chinese Acad Sci, State Key Lab Transducer Technol, Aerosp Informat Res Inst, Beijing 100190, Peoples R China
5.Univ Chinese Acad Sci, Sch Elect Elect & Commun Engn, Beijing 100049, Peoples R China
6.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Guangdong, Peoples R China

Wu, Chengling,Xie, Jingyu,Yao, Qingxin,et al. Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice[J]. ADVANCED MATERIALS,2024,36(27).

Wu, Chengling.,Xie, Jingyu.,Yao, Qingxin.,Song, Yilin.,Yang, Gucheng.,...&Gao, Yuan.(2024).Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice.ADVANCED MATERIALS,36(27).

Wu, Chengling,et al."Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice".ADVANCED MATERIALS 36.27(2024).