Ismail Eman A, Nyandoro Vincent O, Omolo Calvin A, Govender Thirumala
Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, Private Bag X54001, South Africa.
Department of Pharmaceutics, Faculty of Pharmacy, University of Gezira, Wad Medani, Sudan.
Adv Healthc Mater. 2025 Sep;14(23):e2501146. doi: 10.1002/adhm.202501146. Epub 2025 Jul 2.
Sepsis is a life-threatening condition caused by an abnormal immune response to infection, leading to multiple organ failure. 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-inflammatory agents while modulating inflammation by inhibiting PRR-bacterial ligand interactions. This review examines PRR-targeted nanocarriers, focusing on Toll-like receptors (TLRs) and NOD-like 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-targeted nanocarriers in improving sepsis treatment and emphasizes their promise for future clinical application, contingent on further refinement and optimization.
脓毒症是一种由对感染的异常免疫反应引起的危及生命的病症，可导致多器官功能衰竭。尽管在理解其病理生理学方面取得了进展，但仍缺乏治疗脓毒症的有效药物干预措施和纳米药物。模式识别受体（PRR）在检测微生物毒素和引发炎症方面起着关键作用，是细菌性脓毒症及相关器官损伤的有前景的治疗靶点。设计用于靶向PRR的纳米载体可以递送抗生素和抗炎剂，同时通过抑制PRR-细菌配体相互作用来调节炎症。本文综述了靶向PRR的纳米载体，重点关注识别细菌毒素的Toll样受体（TLR）和NOD样受体（NLR）。它评估了所使用的纳米材料、它们的免疫调节作用以及它们在各种体外和体内脓毒症模型中的性能。综述还讨论了当前研究的优势和局限性，为优化纳米载体以获得更好的治疗效果提供了见解。确定了将这些纳米系统转化为临床实践的关键挑战以及加速临床开发的潜在解决方案。总之，该综述强调了靶向PRR的纳米载体在改善脓毒症治疗方面的潜力，并强调了它们在未来临床应用中的前景，这取决于进一步的改进和优化。
