{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:09:45Z","timestamp":1790651385348,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Graft-versus-host disease (GVHD) is a common severe complication of allogeneic hematopoietic stem cell transplant. The current treatments are limited by steroid toxicity, broad immunosuppression, and the potential suppression of the graft-versus-tumor (GVT) effect. Developing less toxic therapies is an unmet need. We previously showed that systemically infused negatively charged immune-modifying microparticles (IMPs) composed of carboxylated poly-lactic-co-glycolic acid are taken up by inflammatory monocytes via the MARCO receptor, reducing symptoms and improving survival in inflammatory conditions. We hypothesized that IMPs could reduce acute GVHD manifestations. Methods: Acute GVHD was induced in an MHC-mismatched murine transplant model with radiation conditioning. IMPs were infused for five days; outcomes were compared to saline controls. We assessed organ histopathology, immune cell populations in the spleen and intestine, serum cytokine levels, and the GVT effect. Results: IMP-treated mice showed significant improvements in terms of clinical GVHD scores, histopathology, and survival. They had increased regulatory T-cells in the spleen and intestine and decreased colonic inflammatory monocytes and cytokines such as IL-6 and IFN-\u03b3. IMPs were ineffective in MARCO knockout mice, confirming receptor dependence. Importantly, GVT activity was preserved, as evidenced by improved survival in mice with A20 lymphoma treated with IMPs. Conclusions: Systemic IMPs reduce clinical GVHD signs and improve survival, likely by decreasing inflammatory monocytes via MARCO and expanded regulatory T-cells numbers, while maintaining GVT activity. These findings support further investigation of IMPs as a targeted GVHD therapy.<\/jats:p>","DOI":"10.3390\/cancers18091431","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:47:28Z","timestamp":1777546048000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myeloid Cell-Targeting PLGA Nanoparticles Ameliorate Acute Graft-Versus-Host Disease"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-0230","authenticated-orcid":false,"given":"John P.","family":"Galvin","sequence":"first","affiliation":[{"name":"University of Illinois Cancer Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara A.","family":"Beddow","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah P.","family":"Lust","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplantation, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"},{"name":"Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0656-5518","authenticated-orcid":false,"given":"Gabriel","family":"Arellano","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Neef","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9359-882X","authenticated-orcid":false,"given":"Adam Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA"},{"name":"Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9556-0718","authenticated-orcid":false,"given":"Stephen D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"},{"name":"Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E56","DOI":"10.1111\/ctr.12065","article-title":"High Readmission Rates Are Associated with a Significant Economic Burden and Poor Outcome in Patients with Grade III\/IV Acute GvHD","volume":"27","author":"Dignan","year":"2013","journal-title":"Clin. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nm915","article-title":"CD4+CD25+ Regulatory T Cells Preserve Graft-versus-Tumor Activity While Inhibiting Graft-versus-Host Disease after Bone Marrow Transplantation","volume":"9","author":"Edinger","year":"2003","journal-title":"Nat. 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