Attenuation of skin injury by a MARCO targeting PLGA nanoparticle.

Autor: Onay UV; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Xu D; Department od Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Biyashev D; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Evans ST; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Demczuk MM; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Neef T; Department od Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Podojil JR; Department od Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Cour Pharmaceutical Development Company, Northbrook, IL, USA., Beddow S; Department od Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Gianneschi NC; Department of Chemistry, Northwestern University, Evanston, IL, USA.; International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center, Northwestern University, Evanston, IL, USA.; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA., Le Poole IC; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Department od Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Miller SD; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. s-d-miller@northwestern.edu.; Department od Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. s-d-miller@northwestern.edu., Lu KQ; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. kurt.lu@northwestern.edu.
Jazyk: angličtina
Zdroj: NPJ Regenerative medicine [NPJ Regen Med] 2024 Dec 06; Vol. 9 (1), pp. 37. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1038/s41536-024-00381-z
Abstrakt: Cutaneous exposure to the DNA alkylating class of chemotherapeutic agents including nitrogen mustard (NM) leads to both skin injury and systemic inflammation. Circulating myeloid subsets recruited to the skin act to further exacerbate local tissue damage while interfering with the wound healing process. We demonstrate herein that intravenous delivery of poly(lactic-co-glycolic acid) immune-modifying nanoparticles (PLGA-IMPs) shortly after NM exposure restricts accumulation of macrophages and inflammatory monocytes at the injury site, resulting in attenuated skin pathology. Furthermore, PLGA-IMPs induce an early influx and local enrichment of Foxp3 + regulatory T cells (Treg) in the skin lesions critical for the suppression of myeloid cell-pro-inflammatory responses via induction of IL-10 and TGF-β in the cutaneous milieu. Functional depletion of CD4 + Tregs ablates the efficacy of PLGA-IMPs accompanied by a loss of local accumulation of anti-inflammatory cytokines essential for wound healing. Thus, in severe skin trauma, PLGA-IMPs may have therapeutic potential via modulation of inflammatory myeloid cells and regulatory T lymphocytes.
Competing Interests: Competing interests: S.D.M. is a co-founder of, member of the Scientific Advisory Board, grantee of, and holds stock options in COUR Pharmaceutical Development Company and on COUR Pharma, Inc., which holds the patent for the PLG nanoparticle technology. J.P. is an employee of COUR Pharmaceutical, Inc. The remaining authors declare no conflicts.
(© 2024. The Author(s).)
Databáze: MEDLINE
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