| Autor: |
Yan‐Qin Geng, Li‐Na Qiu, Yuan‐Qiu Cheng, Juan‐Juan Li, Yi‐Lin Ma, Cheng‐Cheng Zhao, Ying Cai, Xue‐Bin Zhang, Jieli Chen, Yu‐Chen Pan, Ke‐Rang Wang, Xiu‐Hua Yao, Dong‐Sheng Guo, Jia‐Ling Wu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Advanced Science, Vol 11, Iss 24, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202309517 |
| Popis: |
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 to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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