Sulfated Polysaccharide-Based Nanocarrier Drives Microenvironment-Mediated Cerebral Neurovascular Remodeling for Ischemic Stroke Treatment

• DOI: 10.1021/acs.nanolett.4c00650
• Publication Date: 2024-04-23T02:20:16Z
• Authors: Yinli Cao; Yuanman Yu; Lina Pan; Weili Han; Feng Zeng; Jing Wang; Qiyong Mei; Changsheng Liu
• Keywords: Nanocarriers; Stroke; Neurovascular bundle

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, have limited drug release control. Herein, we developed an ROS-responsive nanocarrier targeted delivery the neuroprotective agent rapamycin (RAPA) to mitigate brain damage. The consisted sulfated chitosan (SCS) polymer core modified with boronic ester enveloped by red blood cell membrane shell incorporating homing peptide. When encountering high levels intracellular ROS in tissues, SCS combined RAPA from nanoparticle disintegration facilitates effective microglia polarization and, turn, maintains blood–brain barrier integrity, reduces cerebral infarction, promotes neurovascular remodeling mouse model involving transient middle artery occlusion (tMCAO). This work offers promising strategy treat therapy.