Engineering hirudin encapsulation in pH-responsive antioxidant nanoparticles for therapeutic efficacy in ischemic stroke model mice.

Autor: Mei T; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China., Zhang P; Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China., Hu Y; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China., Xiao L; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China., Hou J; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China., Nagasaki Y; Department of Materials Science, Faculty of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Master's School in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Center for Research in Radiation and Earth System Sciences (CRiES), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Bunkyo-ku, 113-8656, Japan; High-value Biomaterials Research and Commercialization Center (HBRCC), National Taipei University of Technology, Taipei, 10608, Taiwan. Electronic address: happyhusband@nagalabo.jp.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2025 Mar; Vol. 314, pp. 122860. Date of Electronic Publication: 2024 Sep 28.
DOI: 10.1016/j.biomaterials.2024.122860
Abstrakt: This study introduces a novel pH-sensitive, hirudin-loaded antioxidant nanoparticle (HD@iNano AOX ) aimed at addressing the challenges of hirudin's short half-life and hemorrhagic transformation. HD@iNano AOX was engineered to safeguard and prolong hirudin's bioactivity by encapsulating it within antioxidative nanoparticles, facilitating its gradual release in acidic environments. The efficacy of this approach was validated through both ex vivo and in vivo experiments. Ex vivo thrombolytic assays demonstrated that HD@iNano AOX maintained effective clot lysis activity under acidic conditions. In vivo assessments revealed that HD@iNano AOX significantly prolonged hirudin's half-life and reduced cerebral infarct volume in a mouse model of middle cerebral artery occlusion (MCAO). Furthermore, HD@iNano AOX treatment mitigated cerebral oxidative stress, suppressed hemorrhagic transformation, and prevented blood-brain barrier (BBB) disruption. These findings suggest that the combined thrombolytic and antioxidative properties of HD@iNano AOX offer a promising therapeutic approach for ischemic stroke. Nonetheless, further research is warranted to optimize the formulation and assess its safety and efficacy in clinical settings.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this work.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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