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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Modulation of macrophage phenotype via phagocytosis of drug-loaded microparticles
Journal of biomedical materials research. Part A, v 107(6), pp 1213-1224
01 Jun 2019
PMID: 30672109
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Monocyte-derived macrophages play a critical role in directing wound pathology following injury. Depending on their phenotype, macrophages also promote tissue regeneration. However, the therapeutic administration of macrophages with a controlled phenotype is challenging because macrophages are highly plastic and quickly revert to a detrimental, inflammatory phenotype in response to the environment of a damaged tissue. To address this issue, we developed a novel strategy to modulate macrophage phenotype intracellularly through phagocytosis of drug-loaded microparticles. Poly(lactic-co-glycolic acid) microparticles loaded with the anti-inflammatory drug dexamethasone (Dex) were phagocytosed by monocytes and stored intracellularly for at least 5 days. After differentiation into macrophages, cell phenotype was characterized over time with high-throughput gene expression analysis via NanoString. We found that the microparticles modulated macrophage phenotype for up to 7 days after microparticle uptake, with decreases in inflammation-related genes at early timepoints and upregulation of homing- and phagocytosis-related genes at multiple timepoints in a manner similar to cells treated with continuous free Dex. These data suggest that intracellularly loading macrophages with Dex microparticles via phagocytosis could be a unique methodology to selectively modulate macrophage phenotype over time. This strategy would allow therapeutic administration of macrophages for the treatment of a number of inflammatory disease and disorders. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1213-1224, 2019.
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Details
- Title
- Modulation of macrophage phenotype via phagocytosis of drug-loaded microparticles
- Creators
- Kathryn L. Wofford - University of PennsylvaniaD. Kacy Cullen - Center for Neurotrauma, Neurodegeneration and Restoration, CMC VA Medical Center, Philadelphia, Pennsylvania.Kara L. Spiller - Drexel University
- Publication Details
- Journal of biomedical materials research. Part A, v 107(6), pp 1213-1224
- Publisher
- Wiley
- Number of pages
- 12
- Grant note
- I01-RX001097 / Department of Veteran's Affairs; US Department of Veterans Affairs R01HL130037 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Department of Education GAANN iCARE Fellowship R01-HL130037 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) I01RX001097 / Veterans Affairs; US Department of Veterans Affairs
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000467421500010
- Scopus ID
- 2-s2.0-85061440616
- Other Identifier
- 991019168768104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical
- Materials Science, Biomaterials