The role of immunomodulatory nano systems in the treatment of sepsis: past, present, and future

Sepsis is a life-threatening condition caused by a dysregulated host response to infection and remains a leading cause of death in intensive care units. Although antimicrobials and supportive care are vital, patient outcomes are hindered by two conflicting immune states: excessive inflammation and immune paralysis, both contributing to organ failure. Immunomodulatory nanotechnology provides a means to target both aspects of this immune response. Early nanocarriers improved the pharmacokinetics of antibiotics and anti-inflammatory drugs, while modern nanoplatforms enhance this approach with biomimetic coatings, toxin nanosponges, and extracellular vesicles. These tools neutralize Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), modulate Toll-like receptor (TLR) signaling, and reprogram macrophages with spatial and stimulus control. New nanodrugs combine pathway modulation with co-delivery of antimicrobials, and theranostic designs enable treatment tailored to real-time biological data. This review traces the evolution of nanomedicine for sepsis, discussing early advances, current therapies, and future innovations that may hasten clinical application. Literature for this review were searched for through PubMed and Google Scholar (2000-November 2025).