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 |