Review of preclinical EVs for sepsis-associated acute lung injury

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Frontiers in Medicine Published April 18, 2026 Medically reviewed May 25, 2026 Study authors: He Yan, Lin Zhang, Xuejiao Lv, Tingting Guo, Qi Wang, Jie Zhang DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider EVs as a promising preclinical research direction for sepsis-associated acute lung injury.

This publication is a review focusing on the potential of extracellular vesicles (EVs) and EV-inspired biomimetic nanosystems in the context of sepsis-associated acute lung injury. The scope of the article encompasses preclinical research rather than human clinical trials. No specific sample size, population details, or comparator groups are reported within this source. The primary and secondary outcomes, as well as follow-up durations, are not reported in the provided text.

The key argument synthesized by the authors is that EV-based biomimetic nanosystems represent a promising research direction that may complement existing anti-inflammatory strategies. However, the authors explicitly highlight a significant limitation: most available evidence derives from preclinical studies. Because the evidence base is currently preclinical, the review cautions against inferring clinical efficacy from these observations.

Safety data, including adverse events, serious adverse events, discontinuations, and tolerability, are not reported in this review. The authors do not fabricate trial-level detail or invent specific adverse-event rates. The certainty of the findings is constrained by the preclinical nature of the data. Practice relevance is framed cautiously, suggesting these systems are a future possibility rather than a current standard of care.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Sepsis-associated acute lung injury (ALI) remains a major challenge in intensive care units, characterized by dysregulated innate immune responses that drive both excessive inflammation and subsequent immunosuppression. In recent years, extracellular vesicles (EVs) and EV-inspired biomimetic nanosystems have attracted increasing attention as candidate platforms for modulating immune imbalance in ALI. This review summarizes recent advances in understanding the immunopathological mechanisms underlying sepsis-associated ALI, including macrophage polarization imbalance, excessive neutrophil extracellular trap (NET) formation, dendritic cell functional exhaustion, and dysregulation of key signaling pathways such as TLR4, NLRP3 inflammasome, and cGAS–STING. We further discuss how naturally derived EVs and engineered EV-mimetic carriers may influence these pathogenic processes through the delivery of bioactive cargoes, drawing primarily from preclinical observations. In addition, current strategies for pulmonary-targeted delivery, EV engineering approaches, and major translational considerations, including biosafety, manufacturing standardization, and quality control, are critically evaluated. Although most available evidence derives from preclinical studies, EV-based biomimetic nanosystems represent a promising research direction that may complement existing anti-inflammatory strategies by integrating immune modulation, inflammation control, and tissue repair. Continued mechanistic investigation and clinically relevant validation will be essential for determining their therapeutic feasibility in sepsis-associated ALI.