Mesenchymal stem cell-derived apoptotic extracellular vesicles loaded with Prussian blue nanoparticles attenuate severe acute pancreatitis via neutrophil extracellular traps resolution and acinar-ductal metaplasia promot

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Nowadays, severe acute pancreatitis (SAP) remains a critical clinical disease with a high mortality rate. Current treatments are mainly supportive, lacking specific therapies targeting the core pathological mechanisms including neutrophil extracellular traps (NETs)-mediated systemic inflammation and progressive acinar cell necrosis, which may lead to many complications. Therefore, in this study, we developed a novel dual-targeting nanodrug delivery system named PBs@CCR2-ApopEVs, combining Prussian blue nanoparticles (PBs) and CCR2-overexpressing mesenchymal stem cell-derived apoptotic extracellular vesicles (ApopEVs). Through the specific binding of CCR2 with numerous CCL2 released by neutrophils in SAP, the PBs@CCR2-ApopEVs can be actively recruited to the pancreatic inflammation site. Then PBs effectively inhibit neutrophil extracellular trap (NETs) formation by suppressing myeloperoxidase and elastase expression, as well as Gasdermin D pathway activation, thereby reducing oxidative stress and inflammatory responses. Simultaneously, we confirmed that MSCs-ApopEVs could activate the p-STAT3/SOX4 pathway to promote acinar-to-ductal metaplasia (ADM) process, enhancing the self-protection ability of acinar cells and reducing necrosis. This dual-approach strategy-targeting anti-inflammatory effects externally while reinforcing cytoprotective mechanisms internally-stands out as a n

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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