Alleviating Recombinant Tissue Plasminogen Activator-induced Hemorrhagic Transformation in Ischemic Stroke via Targeted Delivery of a Ferroptosis Inhibitor.

ABSTRACT: Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood-brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin-1 (Lip) is proposed to alleviate the side effects. A well-designed macrocyclic carrier, glucose-modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing t

SUBMITTER: Geng YQ 

PROVIDER: S-EPMC11199968 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature