Traditional Chinese Medicine Borneol‐Based Polymeric Micelles Intracerebral Drug Delivery System for Precisely Pathogenesis‐Adaptive Treatment of Ischemic Stroke

Bibliographic Details
Title: Traditional Chinese Medicine Borneol‐Based Polymeric Micelles Intracerebral Drug Delivery System for Precisely Pathogenesis‐Adaptive Treatment of Ischemic Stroke
Authors: Yanan Wang, Xutao Ma, Xinyuan Wang, Liru Liu, Xue Zhang, Qiuyue Wang, Yingfei Zhu, Huanhua Xu, Liangmin Yu, Zhiyu He
Source: Advanced Science, Vol 12, Iss 9, Pp n/a-n/a (2025)
Publisher Information: Wiley, 2025.
Publication Year: 2025
Collection: LCC:Science
Subject Terms: BAPTA‐AM, blood‐brain barrier, borneol, ischemic stroke, ROS‐responsive, Science
More Details: Abstract The scarcity of effective neuroprotective agents and the presence of blood‐brain barrier (BBB)‐mediated extremely inefficient intracerebral drug delivery are predominant obstacles to the treatment of cerebral ischemic stroke (CIS). Herein, ROS‐responsive borneol‐based amphiphilic polymeric NPs are constructed by using traditional Chinese medicine borneol as functional blocks that served as surface brain‐targeting ligand, inner hydrophobic core for efficient drug loading of membrane‐permeable calcium chelator BAPTA‐AM, and neuroprotective structural component. In MCAO mice, the nanoformulation (polymer: 3.2 mg·kg−1, BAPTA‐AM: 400 µg·kg−1) reversibly opened the BBB and achieved high brain biodistribution up to 12.7%ID/g of the total administered dose after 3 h post single injection, effectively restoring intracellular Ca2+ and redox homeostasis, improving cerebral histopathology, and inhibiting mitochondrial PI3K/Akt/Bcl‐2/Bax/Cyto‐C/Caspase‐3,9 apoptosis pathway for rescuing dying neurons (reduced apoptosis cell from 59.5% to 7.9%). It also remodeled the inflammatory microenvironment in cerebral ischemic penumbra by inhibiting astrocyte over‐activation, reprogramming microglia polarization toward an anti‐inflammatory phenotype, and blocking NF‐κB/TNF‐α/IL‐6 signaling pathways. These interventions eventually reduced the cerebral infarction area by 96.3%, significantly improved neurological function, and restored blood flow reperfusion from 66.2% to ≈100%, all while facilitating BBB repair and avoiding brain edema. This provides a potentially effective multiple‐stage sequential treatment strategy for clinical CIS.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2198-3844
Relation: https://doaj.org/toc/2198-3844
DOI: 10.1002/advs.202410889
Access URL: https://doaj.org/article/eb92bc376b49461ebd23b89e17bb8601
Accession Number: edsdoj.b92bc376b49461ebd23b89e17bb8601
Database: Directory of Open Access Journals
More Details
ISSN:21983844
DOI:10.1002/advs.202410889
Published in:Advanced Science
Language:English