1. Reprogramming monocytes into M2 macrophages as living drug depots to enhance treatment of myocardial ischemia-reperfusion injury.
- Author
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Liu Y, Zhou M, Xu M, Wang X, Zhang Y, Deng Y, Zhang Z, Jiang J, Zhou X, and Li C
- Subjects
- Animals, Mice, Male, Ferrocyanides chemistry, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents pharmacology, Drug Carriers chemistry, Cellular Reprogramming drug effects, Reactive Oxygen Species metabolism, Myocardial Reperfusion Injury drug therapy, Macrophages drug effects, Nanoparticles chemistry, Monocytes drug effects, Betamethasone administration & dosage, Betamethasone analogs & derivatives, Mice, Inbred C57BL
- Abstract
Delivering therapeutic agents efficiently to inflamed regions remains an intractable challenge following myocardial ischemia-reperfusion injury (MI/RI) due to the transient nature of the enhanced permeability and retention effect, which disappears after 24 h. Leveraging the inflammation-homing and plasticity properties of circulating monocytes (MN) as hitchhiking carriers and further inducing their polarization into anti-inflammatory phenotype macrophages upon reaching the inflamed sites is beneficial for MI/RI therapy. Herein, DSS/PB@BSP nanoparticles capable of clearing reactive oxygen species and inhibiting inflammation were developed by employing hollow Prussian blue nanoparticles (PB) as carriers to encapsulate betamethasone sodium phosphate (BSP) and further modified with dextran sulfate sodium (DSS), a targeting ligand for the scavenger receptor on MN. This formulation was internalized into MN as living cell drug depots, reprogramming them into anti-inflammation type macrophages to inhibit inflammation. In vitro assessments revealed the successful construction of the nanoparticle. In a murine MI/RI model, circulating MN laden with these nanoparticles significantly enhanced drug delivery and accumulation at the cardiac injury site, exhibiting favorable therapeutic ability and promoting M2-biased differentiation. Our study provides an effective approach with minimally invasion and biosecurity that makes this nanoplatform as a promising candidate for immunotherapy and clinical translation in the treatment of MI/RI., Competing Interests: Declaration of competing interest The author reports no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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