Intrahippocampal Supramolecular Assemblies Directed Bioorthogonal Liberation of Neurotransmitters to Suppress Seizures in Freely Moving Mice.
Adv Mater
; 36(27): e2314310, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38655719
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Seizures
/
Reactive Oxygen Species
/
Neurotransmitter Agents
/
Gamma-Aminobutyric Acid
/
Hippocampus
Limits:
Animals
Language:
En
Journal:
Adv Mater
/
Adv. mater. (Weinheim Print)
/
Advanced materials (Weinheim Print)
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Alemania