Affiliation:
1. School of Medicine Chongqing University 131 Yubei Street, Shapingba District Chongqing 400044 China
2. Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University 83 Shabei Street, Shapingba District Chongqing 400030 China
Abstract
AbstractOxidative stress induced by ischemia‐reperfusion causes severe secondary injury in stroke patients. The blood‐brain barrier (BBB) and the challenges in targeting the stroke core hinder the therapeutic effect of drugs. This study introduces a precise biomimetic drug delivery system called SHp‐NM@Edv/RCD (SNM‐NPs), which possesses multiple stepwise targeting capabilities. SNM‐NPs are encapsulated by the neutrophil membranes (NMs) and exhibit a targeting effect (5.16‐fold) on the inflammatory microenvironment. The modification of stroke‐homing peptides (SHp) makes SNM‐NPs target damaged neurons faster, with a targeting efficiency 5.68 times higher than that of β‐cyclodextrins (RCD). Then, RCD encapsulated in SNM‐NPs responds to reactive oxygen species (ROS), leading to the release of edaravone (Edv), scavenges ROS, inhibits neuroinflammation, and reduces neuronal apoptosis by 90%. Mechanistically, SNM‐NPs deliver Edv precisely to the cerebral ischemia‐reperfusion injury (CIRI) site, resulting in the elimination of ROS, a decrease in the number of microglia, an improvement in tubulin expression in neurons, and the inhibition of neuronal apoptosis through Caspase 3 pathway. Preliminary experiments also show that SNM‐NPs exhibit a good safety profile both in intravenous therapy and in vitro cell experiments. As a result, SNM‐NPs hold promise for further development as effective and safe agents for target therapy of CIRI and other diseases.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
8 articles.
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