Attenuation of skin injury by a MARCO targeting PLGA nanoparticle
Abstract 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 hea...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-024-00381-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850137110418292736 |
|---|---|
| author | Ummiye V. Onay Dan Xu Dauren Biyashev Spencer T. Evans Michael M. Demczuk Tobias Neef Joseph R. Podojil Sara Beddow Nathan C. Gianneschi I. Caroline Le Poole Stephen D. Miller Kurt Q. Lu |
| author_facet | Ummiye V. Onay Dan Xu Dauren Biyashev Spencer T. Evans Michael M. Demczuk Tobias Neef Joseph R. Podojil Sara Beddow Nathan C. Gianneschi I. Caroline Le Poole Stephen D. Miller Kurt Q. Lu |
| author_sort | Ummiye V. Onay |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-ee72089f6b5b4526b932dafa4b2f485a |
| institution | OA Journals |
| issn | 2057-3995 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj-art-ee72089f6b5b4526b932dafa4b2f485a2025-08-20T02:30:56ZengNature Portfolionpj Regenerative Medicine2057-39952024-12-019111110.1038/s41536-024-00381-zAttenuation of skin injury by a MARCO targeting PLGA nanoparticleUmmiye V. Onay0Dan Xu1Dauren Biyashev2Spencer T. Evans3Michael M. Demczuk4Tobias Neef5Joseph R. Podojil6Sara Beddow7Nathan C. Gianneschi8I. Caroline Le Poole9Stephen D. Miller10Kurt Q. Lu11Department of Dermatology, Feinberg School of Medicine, Northwestern UniversityDepartment od Microbiology-Immunology, Feinberg School of Medicine, Northwestern UniversityDepartment of Dermatology, Feinberg School of Medicine, Northwestern UniversityDepartment of Dermatology, Feinberg School of Medicine, Northwestern UniversityDepartment of Dermatology, Feinberg School of Medicine, Northwestern UniversityDepartment od Microbiology-Immunology, Feinberg School of Medicine, Northwestern UniversityDepartment od Microbiology-Immunology, Feinberg School of Medicine, Northwestern UniversityDepartment od Microbiology-Immunology, Feinberg School of Medicine, Northwestern UniversityDepartment of Chemistry, Northwestern UniversityDepartment of Dermatology, Feinberg School of Medicine, Northwestern UniversityDepartment of Dermatology, Feinberg School of Medicine, Northwestern UniversityDepartment of Dermatology, Feinberg School of Medicine, Northwestern UniversityAbstract 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.https://doi.org/10.1038/s41536-024-00381-z |
| spellingShingle | Ummiye V. Onay Dan Xu Dauren Biyashev Spencer T. Evans Michael M. Demczuk Tobias Neef Joseph R. Podojil Sara Beddow Nathan C. Gianneschi I. Caroline Le Poole Stephen D. Miller Kurt Q. Lu Attenuation of skin injury by a MARCO targeting PLGA nanoparticle npj Regenerative Medicine |
| title | Attenuation of skin injury by a MARCO targeting PLGA nanoparticle |
| title_full | Attenuation of skin injury by a MARCO targeting PLGA nanoparticle |
| title_fullStr | Attenuation of skin injury by a MARCO targeting PLGA nanoparticle |
| title_full_unstemmed | Attenuation of skin injury by a MARCO targeting PLGA nanoparticle |
| title_short | Attenuation of skin injury by a MARCO targeting PLGA nanoparticle |
| title_sort | attenuation of skin injury by a marco targeting plga nanoparticle |
| url | https://doi.org/10.1038/s41536-024-00381-z |
| work_keys_str_mv | AT ummiyevonay attenuationofskininjurybyamarcotargetingplgananoparticle AT danxu attenuationofskininjurybyamarcotargetingplgananoparticle AT daurenbiyashev attenuationofskininjurybyamarcotargetingplgananoparticle AT spencertevans attenuationofskininjurybyamarcotargetingplgananoparticle AT michaelmdemczuk attenuationofskininjurybyamarcotargetingplgananoparticle AT tobiasneef attenuationofskininjurybyamarcotargetingplgananoparticle AT josephrpodojil attenuationofskininjurybyamarcotargetingplgananoparticle AT sarabeddow attenuationofskininjurybyamarcotargetingplgananoparticle AT nathancgianneschi attenuationofskininjurybyamarcotargetingplgananoparticle AT icarolinelepoole attenuationofskininjurybyamarcotargetingplgananoparticle AT stephendmiller attenuationofskininjurybyamarcotargetingplgananoparticle AT kurtqlu attenuationofskininjurybyamarcotargetingplgananoparticle |