Protein-Carbon Dot Nanohybrid-Based Early Blood-Brain Barrier Damage Theranostics

ACS Appl Mater Interfaces. 2020 Jan 22;12(3):3445-3452. doi: 10.1021/acsami.9b19378. Epub 2020 Jan 10.

Abstract

For effective treatment of ischemic cerebral thrombosis, it is of great significance to find a facile way in assessing the early damage of blood-brain barrier (BBB) after ischemic stroke during thrombolysis by integrating thrombolytic agents with fluorescent materials. Herein, a novel type of protein-carbon dot nanohybrids is reported by the incorporation of carbon dots on thrombolytic agents through covalent linkage. Both in vitro and ex vivo fluorescence imaging measurements have demonstrated remarkable imaging effects in the brain of transient middle cerebral artery occlusion mice. Besides, the outstanding thrombolytic capacity of the nanohybrids was determined by in vitro thrombolysis tests. As one of the few reports of the construction of thrombolytic agents and fluorescent nanomaterials, the nanohybrids retain thrombolysis ability and fluorescent traceability simultaneously. It may provide a promising indicator for early BBB damage and thrombolytic agent distribution to estimate the possibility of symptomatic intracranial hemorrhage after thrombolysis and supply tissue window evidence for clinical thrombolytic agent application.

Keywords: blood−brain barrier; carbon dots; fluorescence imaging; protein; thrombolysis.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Carbon / chemistry*
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / chemistry
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanostructures / chemistry*
  • Stroke / diagnostic imaging
  • Stroke / drug therapy*
  • Theranostic Nanomedicine / instrumentation
  • Theranostic Nanomedicine / methods*
  • Urokinase-Type Plasminogen Activator / administration & dosage*
  • Urokinase-Type Plasminogen Activator / chemistry

Substances

  • Fibrinolytic Agents
  • Carbon
  • Urokinase-Type Plasminogen Activator