Prussian blue nanozyme

Hepatic fibrosis, a progressive pathological condition driven by oxidative stress, chronic inflammation, and hepatic stellate cell (HSC) activation, represents a critical unmet medical need with a current lack of effective therapeutic interventions. Herein, we present Prussian blue (PB) nanozymes as an innovative multifunctional nanotherapeutic platform engineered to simultaneously disrupt the pathogenic triad driving fibrogenesis. These PB nanozymes exhibited a well-defined crystalline structure with pronounced multifunctional enzymatic cascade activities, demonstrating peroxidase-, superoxide dismutase-, and catalase-like catalytic competencies, along with hydroxyl radical scavenging efficiency of 70 ± 5%. In vitro studies revealed that PB nanozymes suppressed LPS-induced pro-inflammatory cytokine secretion while attenuating TGF-β-mediated Collagen-1/α-SMA upregulation in activated HSCs. In a murine model of carbon tetrachloride-induced hepatic fibrosis, pretreatment with PB nanozymes significantly attenuated the elevation of serum alanine aminotransferase and aspartate aminotransferase levels, reduced hepatic hydroxyproline accumulation, and improved histopathological fibrosis scores. Mechanistic investigations demonstrated significant suppression of HSC activation markers concomitant with reduced collagen deposition in fibrotic livers. Notably, PB nanozymes exhibited superior biocompatibility profiles and demonstrated selective hepatic accumulation through enhanced permeability and retention effects. The PB nanozyme platform demonstrates a therapeutically synergistic triad mechanism comprising reactive oxygen species (ROS) scavenging, immunomodulatory intervention, and HSC quiescence induction. Preclinical evaluation reveals an optimized pharmacokinetic profile with sustained bioavailability and favorable toxicological parameters, establishing PB nanozymes as a promising therapeutic strategy for fibrotic liver disease management.

Sepsis is a life-threatening condition involving dysfunctional organ responses stemming from dysregulated host immune reactions to various infections. The lungs are most prone to failure during sepsis, resulting in acute lung injury (ALI). ALI is associated with oxidative stress and inflammation, and current therapeutic strategies are limited. To develop a more specific treatment, this study aimed to synthesise Prussian blue nanozyme (PBzyme), which can reduce oxidative stress and inflammation, to alleviate ALI. PBzyme with good biosafety was synthesised using a modified hydrothermal method. PBzyme was revealed to be an activator of haem oxygenase-1 (HO-1), improving survival rate and ameliorating lung injury in mice. Zinc protoporphyrin, an inhibitor of HO-1, inhibited the prophylactic therapeutic efficacy of PBzyme on ALI, and affected the nuclear factor-κB signaling pathway and activity of HO-1. This study demonstrates that PBzyme can alleviate oxidative stress and inflammation through HO-1 and has a prophylactic therapeutic effect on ALI. This provides a new strategy and direction for the clinical treatment of sepsis-induced ALI.