Pathological Signal-Responsive Nanoplatforms for Sepsis: Integrating Biomarker Sensing With Spatiotemporal Drug Delivery and Immunomodulation.

Sepsis remains a life-threatening syndrome characterized by dynamic immune dysregulation and multi-organ failure. Stimulus-responsive nanoplatforms, which function as "biomarker-triggered" therapeutic systems, have emerged as a frontier in precision sepsis management. These platforms are engineered to autonomously sense pathological hallmarks within the sepsis microenvironment-such as fluctuations in pH, reactive oxygen species (ROS), and specific enzymatic over-expression-thereby enabling precise, spatiotemporal drug release. Unlike conventional static therapies, these "smart" nanoplatforms modulate therapeutic intervention in real-time based on disease progression. This review comprehensively evaluates the integration of sensing and therapy using nanoplatforms loaded with antibiotics, antimicrobial peptides, anti-inflammatory agents, and gene-regulatory molecules. We highlight how these platforms optimize therapeutic windows by enhancing local drug bioavailability while minimizing systemic off-target toxicity. Furthermore, we discuss the current hurdles in clinical translation, including patient-specific biomarker variability and the complexity of scalable fabrication. Finally, we propose future directions, emphasizing the synergy of real-time biosensing, artificial intelligence (AI), and multimodal "theranostic" platforms to achieve stage-specific, personalized interventions. These advancements hold the potential to redefine sepsis management by shifting from "one-size-fits-all" treatments to biomarker-driven precision medicine.