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Therefore, new therapeutic strategies that maintain high efficacy while minimizing adverse effects are essential. Although nanomedicine has advanced systemic and kidney-targeted drug delivery, a reliable method for glomerulus-specific delivery is lacking. Collagen IV (Col4)-alpha 3, located in the glomerular basement membrane at the blood\u2013tissue interface through fenestrated capillary endothelium, represents an ideal target for glomeruli delivery. Herein, we developed a novel liposomal nanoparticle conjugated with a Col4-alpha 3-binding peptide (Col4-\u03b13-NPs) for selective glomerular targeting. Prednisolone-loaded Col4-\u03b13-NPs were administered to lupus-prone mice twice weekly for 8\u00a0weeks. Kidney injury and function were evaluated biweekly, and renal immune cell populations were analyzed by flow cytometry at study completion. The results show that rhodamine-labeled NPs predominantly accumulate in kidney glomeruli 48\u00a0h after intravenous injection. The Col4-NP system demonstrated stable and prolonged release of the encapsulated drug for over 48\u00a0h. Lupus-prone mice treated with prednisolone-loaded Col4-NPs showed significantly improved renal function and histology, including a 30% increase in glomerular filtration rate, a 56% reduction in proteinuria, and decreased IgG deposition and fibrosis. Notably, treatment also enhanced renal regulatory T cell populations. These findings suggest that glomerulus-targeted Col4-\u03b13-NPs hold significant translational promise. This platform may offer an effective, site-specific treatment for LN while minimizing systemic side effects and could be adapted for other glomerular diseases requiring targeted therapy.<\/jats:p>","DOI":"10.1042\/cs20261409","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:34:06Z","timestamp":1785940446000},"page":"1895-1913","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glomerulus-targeted nanotherapy via collagen IV-\u03b13 binding enhances renal immunoregulation in lupus nephritis"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0181-0043","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"1Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL 33612, U.S.A."},{"name":"8University of South Florida Health Transplant Research 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U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Sharma","sequence":"additional","affiliation":[{"name":"3Center for Immunity Inflammation and Regenerative Medicine, Division of Nephrology, University of Virginia School of Medicine, Charlottesville, VA 22903, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Esquivel","sequence":"additional","affiliation":[{"name":"1Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshata","family":"Patne","sequence":"additional","affiliation":[{"name":"2Laboratory for Translational Nanotechnology and Institute of Translational Virology and Innovation, Department of Internal Medicine, University of South Florida, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wei","sequence":"additional","affiliation":[{"name":"4Division of Nephrology, Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"4Division of Nephrology, Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristof","family":"Williams","sequence":"additional","affiliation":[{"name":"1Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Lawless","sequence":"additional","affiliation":[{"name":"5Department of Molecular Medicine, University 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U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhra","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"5Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, U.S.A."},{"name":"6James A Haley Veterans Hospital, Research Service, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"2Laboratory for Translational Nanotechnology and Institute of Translational Virology and Innovation, Department of Internal Medicine, University of South Florida, Tampa, FL 33612, U.S.A."},{"name":"6James A Haley Veterans Hospital, Research Service, Tampa, FL 33612, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruisheng","family":"Liu","sequence":"additional","affiliation":[{"name":"1Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL 33612, 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