Angiopep-2 Modified Exosomes Load Rifampicin with Potential for Treating Central Nervous System Tuberculosisстатья из журнала
Аннотация: Background: Central nervous system tuberculosis (CNS-TB) is the most devastating form of extrapulmonary tuberculosis. Rifampin (RIF) is a first-line antimicrobial agent with potent bactericidal action. Nonetheless, the blood-brain barrier (BBB) limits the therapeutic effects on CNS-TB. Exosomes, however, can facilitate drug movements across the BBB. In addition, exosomes show high biocompatibility and drug-loading capacity. They can also be modified to increase drug delivery efficacy. In this study, we loaded RIF into exosomes and modified the exosomes with a brain-targeting peptide to improve BBB permeability of RIF; we named these exosomes ANG-Exo-RIF. Methods: Exosomes were isolated from the culture medium of BMSCs by differential ultracentrifugation and loaded RIF by electroporation and modified ANG by chemical reaction. To characterize ANG-Exo-RIF, Western blot (WB), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were performed. Bend.3 cells were incubated with DiI labeled ANG-Exo-RIF and then fluorescent microscopy and flow cytometry were used to evaluate the targeting ability of ANG-Exo-RIF in vitro. Fluorescence imaging and frozen section were used to evaluate the targeting ability of ANG-Exo-RIF in vivo. MIC and MBC were determined through microplate alamar blue assay (MABA). Results: A novel exosome-based nanoparticle was developed. Compared with untargeted exosomes, the targeted exosomes exhibited high targeting capacity and permeability in vitro and in vivo. The MIC and MBC of ANG-Exo-RIF were 0.25 μg/mL, which were sufficient to meet the clinical needs. Conclusion: In summary, excellent targeting ability, high antitubercular activity and biocompatibility endow ANG-Exo-RIF with potential for use in future translation-aimed research and provide hope for an effective CNS-TB treatment. Graphical Abstract: Keywords: exosome, central nervous system tuberculosis, blood-brain barrier, rifampin
Год издания: 2023
Авторы: Han Li, Yinan Ding, Jiayan Huang, Yanyan Zhao, Wei Chen, Qiusha Tang, Yanli An, Rong Chen, Chunmei Hu
Издательство: Dove Medical Press
Источник: International Journal of Nanomedicine
Ключевые слова: Extracellular vesicles in disease, Bacterial Infections and Vaccines, Lipid Membrane Structure and Behavior
Другие ссылки: International Journal of Nanomedicine (PDF)
International Journal of Nanomedicine (HTML)
PubMed Central (HTML)
PubMed (HTML)
International Journal of Nanomedicine (HTML)
PubMed Central (HTML)
PubMed (HTML)
Открытый доступ: gold
Том: Volume 18
Страницы: 489–503