Nanocarrier-Based Targeting of Pattern Recognition Receptors as an Innovative Strategy for Enhancing Sepsis Therapy

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.