Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement

Shuyan Zheng, Ying Ying Bai, Yikang Liu, Xihui Gao, Yan Li, Yinzhi Changyi, Yuancheng Wang, Di Chang, Shenghong Ju, Cong Li

Research output: Contribution to journalArticlepeer-review

Abstract

Ischemic stroke is a leading cause of adult disability and cognitive impairment worldwide. Neuroprotective therapy aims to save neurons by impeding the deleterious ischemic insults. However, the low efficiency of the neuroprotectants crossing blood brain barrier (BBB) prevents their clinical translation. In this work, a nanoagonist (NA) was developed to enhance neuroprotectant uptake by specifically increasing BBB permeability in brain ischemia. This NA first targeted ischemic brain vasculatures, temporarily opened local BBB by activating adenosine 2A receptors, and up-regulated the neuroprotectant uptake in brain ischemia. This NA significantly increased the delivery of superoxide dismutase (SOD), a free radical scavenger, into mouse brain ischemia. The combined treatment of NA/SOD achieved a five-fold ischemic volume reduction rate compared to the animal models treated with SOD alone. Non-invasive magnetic resonance imaging (MRI) confirmed the ischemia targeted BBB opening, increased brain drug delivery efficiency and up-regulated therapeutic response during the combined NA/SOD treatment. Since the inefficient brain drug delivery is a general problem for the treatment of central nervous system (CNS) diseases, this work provides a novel strategy to deliver therapeutics by crossing BBB with high efficiency and targeting specificity.

Original languageEnglish (US)
Pages (from-to)9-20
Number of pages12
JournalBiomaterials
Volume66
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • Adenosine receptor
  • Blood brain barrier
  • Ischemic stroke
  • Nanoagonist
  • Neuroprotective therapy

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Fingerprint Dive into the research topics of 'Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement'. Together they form a unique fingerprint.

Cite this