PUBLICATION

An Implant-Free Nanosystem Enabling Synergistic Oxidative Damage Mitigation and Deep Brain Stimulation for Alleviating Parkinsonian Symptoms

Authors
Zhou, C., Wu, F., He, L., Yan, H., Zhang, Z., Zhao, S., Huang, W., Luo, Y., Zhao, W., Gao, B., Zhang, Z., Zhou, Y., Wu, B., Liu, J., Zhu, D.
ID
ZDB-PUB-250716-7
Date
2025
Source
ACS nano : (Journal)
Registered Authors
Keywords
Ca2+ signaling, cascade nanozyme, deep brain stimulation, implant-free, oxidative stress mitigation, photothermal activation
MeSH Terms
  • Oxides
  • Nanoparticles*/chemistry
  • Reactive Oxygen Species/metabolism
  • Manganese Compounds/chemistry
  • Manganese Compounds/pharmacology
  • Polymers/chemistry
  • Deep Brain Stimulation*
  • Animals
  • Oxidative Stress*/drug effects
  • Indoles/chemistry
  • Humans
  • Parkinson Disease*/metabolism
  • Parkinson Disease*/therapy
  • Zebrafish
PubMed
40664603 Full text @ ACS Nano
Abstract
Deep brain stimulation (DBS) effectively alleviates motor symptoms in Parkinson's disease (PD) patients; however, it necessitates permanent invasive implantation of conduits, and its therapeutic effects diminish as PD progresses. Herein, an implant-free NIR-II laser-activated intervention nanosystem that combines wireless DBS with antioxidative neuroprotection is developed to overcome the above challenges. Enzyme-like 2-(phenylselanyl)ethan-1-amine (SePh) and manganese dioxide (MnO2) and NIR-II absorber IR-1048 (IR) are integrated onto the mesoporous polydopamine (mPDA) core to form mPDA-SeMn-IR. Upon NIR-II laser irradiation, intraventricularly injected mPDA-SeMn-IR nanoparticles effectively activate endogenously expressed inositol 1,4,5-trisphosphate receptors, leading to Ca2+ outflux from the endoplasmic reticulum. Ca2+ signaling enhances tyrosine hydroxylase expression and activity and triggers dopamine release to enhance dopaminergic function. Meanwhile, mPDA-SeMn-IR rapidly eliminates excessive reactive oxygen species, synergistically enhancing long-term DBS efficiency by increasing neuron survival and restoring neuronal function for improved dopamine secretion. In vivo, mPDA-SeMn-IR regulates midbrain neurons and coiling behaviors in zebrafish and considerably alleviates motor symptoms in the PD model, proposing a promising therapeutic strategy to address existing challenges in PD therapies.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping