Hypoxia-responsive calixarene-grafted self-assembled peptide hydrogel for inflammation suppression in ischemic stroke

Abstract

Hypoxia is a significant characteristic of ischemic stroke. Recently, development of the pathology of tissue injury and deployment of new hypoxia-responsive technologies provide further opportunity for the application of hypoxia-responsive materials beyond cancer. To fully take advantage of hypoxic pathological feature of stroke and make advancement of stroke therapy, a hypoxia-responsive self-assembled peptide hydrogel was prepared for inflammation suppression in ischemic stroke treatment, utilizing azocalixarene (CA) as a hypoxia-responsive controlled release drug carrier. After induction of PBS, the peptide hydrogel was fabricated with brain-similar rheological modulus and shear-thinning property. The hypoxia-responsive performance of the peptide hydrogel was validated by three hypoxia & reductase systems including sodium hydrosulfite (SDT), rat liver microsomes and oxygen-glucose deprivation model (OGD) to achieve the responsive release of Cyanine 5-dimethyl (CY5-DM) or Fingolimod (FTY720) in vitro. After local administration of the hypoxia-responsive self-assembled peptide hydrogel, the improved motor function, reduced infarct volume and alleviated inflammation were achieved, revealing the effective stroke therapy in vivo.