基金support from the National Key Research and Development Program of China(No.2022YFD1800900)the Fundamental Research Funds for the Central Universities(No.2662024HXPY002)+2 种基金State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(No.SKLCUSA-b202301)the Hubei Province Chinese Medicine Research Project(No.ZY2025Q026)the Medical Young Talents Program of Hubei Province to L.-L.B.
文摘Due to its complex pathogenesis involving dysregulated reactive oxygen species(ROS)storms,cytokine hyperactivation and immune cell infiltration,acute lung injury(ALI)presents critical clinical challenges,and conventional therapies often fail to address the dual requirements of precise inflammatory targeting and microenvironment regulation.Herein,we report an intelligent biomimetic nanosystem(CeGM)featuring(i)synergistic catalytic circuits,where hollow CeO_(2)nanoenzymes are combined with glycyrrhizic acid(GA)through density functional theory(DFT)-optimized binding configurations,achieving charge redistribution-induced dual-site catalytic activation relative to conventional CeO_(2)alone;(ii)pathology-responsive delivery,where macrophage membrane camouflage enables lipopolysaccharide(LPS)recognition and inflammatory chemotaxis,yielding 7.8-fold higher alveolar accumulation than non-coated counterparts in LPS-induced ALI models;(iii)multidimensional immunomodulation,where NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome activation(56.20%interleukin-1β(IL-1β)reduction)and M1 macrophage polarization(2.4-fold M2/M1 ratio increase)are concurrently suppressed through GA-mediated nuclear factor kappa B(NF-κB)pathway inhibition and CeO_(2)-mediated redox homeostasis restoration.This dual-functional nanoplatform demonstrates favourable therapeutic outcomes in mitigating pulmonary edema by clearing ROS(47.20%reduction in ROS levels),neutrophil infiltration(58.16%myeloperoxidase(MPO)activity decrease)and cytokine storms(tumor necrosis factor-alpha(TNF-α)reduction of 45.90%),offering a paradigm-shifting strategy for precision nanomedicine in acute inflammatory disorders.
