Cellular hitchhiking of selenium carbon dots for targeted macrophage polarization in acute lung injury

Acute lung injury (ALI) is a life-threatening pulmonary disorder characterized by dysregulated inflammatory responses, excessive activation of pro-inflammatory M1 macrophages, severe oxidative stress, and potentially fatal cytokine storms. Conventional therapies are severely limited by poor targeting of the inflammatory microenvironment and insufficient cellular uptake by hyperactivated immune cells. To address these translational barriers, we developed a "cellular hitchhiking" nanoplatform by coating selenium-doped carbon quantum dots (SC) with bacterial outer membrane vesicles (OMVs) derived from the probiotic Escherichia coli Nissle 1917. This biomimetic nanoparticle (SC@OMV) leverages pathogen-associated molecular patterns naturally present in OMVs to achieve precise targeted delivery and highly efficient internalization by pulmonary macrophages via pattern recognition receptors. Following cellular uptake, SC efficiently scavenges excessive reactive oxygen species and promotes macrophage repolarization from the pro-inflammatory M1 phenotype toward the tissue-reparative M2 phenotype. In vivo evaluations using an LPS-induced ALI mouse model demonstrated that intravenously administered SC@OMVs preferentially accumulate in inflamed lung tissues. Moreover, SC@OMVs effectively suppressed cytokine storms and promoted the repair of the alveolar-capillary barrier by modulating the TLR4/MyD88/NF-κB signaling pathway. By synergistically integrating the targeted biological delivery capabilities of OMVs with the potent intracellular immunomodulatory and antioxidant properties of selenium, the use of SC@OMVs represents a highly promising, precise therapeutic strategy for the comprehensive management of ALI.