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Despite advances in understanding its pathophysiology, effective pharmacological interventions and nanomedicines to treat sepsis remain lacking. Pattern recognition receptors (PRRs), crucial in detecting microbial toxins and triggering inflammation, are promising therapeutic targets for bacterial sepsis and related organ injuries. Nanocarriers designed to target PRRs can deliver antibiotics and anti\u2010inflammatory agents while modulating inflammation by inhibiting PRR\u2010bacterial ligand interactions. This review examines PRR\u2010targeted nanocarriers, focusing on Toll\u2010like receptors (TLRs) and NOD\u2010like receptors (NLRs), which recognize bacterial toxins. It evaluates the nanomaterials used, their immunomodulatory effects, and their performance in various in vitro and in vivo sepsis models. The review also discusses the strengths and limitations of current research, offering insights into optimizing nanocarriers for better therapeutic outcomes. Key challenges in translating these nanosystems into clinical practice are identified, alongside potential solutions for accelerating clinical development. In conclusion, the review highlights the potential of PRR\u2010targeted nanocarriers in improving sepsis treatment and emphasizes their promise for future clinical application, contingent on further refinement and optimization.<\/jats:p>","DOI":"10.1002\/adhm.202501146","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:11:17Z","timestamp":1751429477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nanocarrier\u2010Based Targeting of Pattern Recognition Receptors as an Innovative Strategy for Enhancing Sepsis Therapy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8725-3198","authenticated-orcid":false,"given":"Eman A.","family":"Ismail","sequence":"first","affiliation":[{"name":"Discipline of Pharmaceutical Sciences College of Health Sciences University of KwaZulu\u2010Natal  Durban Private Bag X54001 South Africa"},{"name":"Department of Pharmaceutics Faculty of Pharmacy University of Gezira  Wad Medani Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent O.","family":"Nyandoro","sequence":"additional","affiliation":[{"name":"Discipline of Pharmaceutical Sciences College of Health Sciences University of KwaZulu\u2010Natal  Durban Private Bag X54001 South Africa"},{"name":"Department of Pharmaceutics and Pharmaceutical Chemistry School of Pharmacy Kabarak University  Kabarak Private Bag 20157 Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin A.","family":"Omolo","sequence":"additional","affiliation":[{"name":"Discipline of Pharmaceutical Sciences College of Health Sciences University of KwaZulu\u2010Natal  Durban Private Bag X54001 South Africa"},{"name":"Department of Pharmaceutics School of Pharmacy and Health Sciences United States International University\u2010Africa  Nairobi P.O. 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