Integrated cascade catalysis of microalgal bioenzyme and inorganic nanozyme for anti-inflammation therapy.

Combinations of multiple enzymes for cascade catalysis have been widely applied in biomedicine, but the integration of a natural bioenzyme with an inorganic nanozyme is less developed. Inspired by the abundant content of superoxide dismutase (SOD) in Spirulina platensis (SP), we establish an integrated cascade catalysis for anti-inflammation therapy by decorating catalase (CAT)-biomimetic ceria nanoparticles (CeO2) onto the SP surface via electrostatic interaction to build microalgae-based biohybrids. The biohybrids exhibit combined catalytical competence for preferentially transforming superoxide anion radicals (O2˙-) to hydrogen peroxide (H2O2), and subsequently catalyzing H2O2 disproportionation to water and oxygen. In ulcerative colitis and Crohn's disease, the biohybrids reveal a satisfactory therapeutic effect owing to the synergistic reactive oxygen species (ROS)-scavenging capacity, suggesting a new train of thought for enzyme-based biomedical application.

Hierarchy-Assembled Dual Probiotics System Ameliorates Cholestatic Drug-Induced Liver Injury via Gut-Liver Axis Modulation.

Cholestatic drug-induced liver injury (DILI) induced by drugs or other xenobiotics is a severe and even fatal clinical syndrome. Here, living materials of hierarchy-assembled dual probiotics system are fabricated by sequentially encapsulating probiotic Lactobacillus delbrueckii subsp. bulgaricus (LDB) and Lactobacillus rhamnosus GG (LGG) into Ca2+ -complexed polymer microspheres for effective prevention of cholestatic DILI. Upon entering intestinal tract of the constructed living materials, LGG is released because of pH-triggered dissolution of outer enteric polymer coating. The released LGG can inhibit hepatic bile acids (BAs) synthesis by activating intestinal farnesoid X receptor-fibroblast growth factor 15（FGF-15) signaling pathway. BAs excretion is also facilitated by LGG through increasing the abundance of bile salt hydrolase (BSH)-active gut commensal bacteria. Furthermore, exposed positively-charged chitosan shell can absorb the excessive BAs via electrostatic interaction, which leads to steady BAs fixation by the imprisoned LDB, decreasing the total BAs amounts in enterohepatic circulation. Together, the fabricated living materials, obtained here, can effectively prevent cholestatic DILI through dredging cholestasis via gut-liver axis modulation. The therapeutic effect is demonstrated in α-naphthylisothiocyanate and clinical antiepileptic drug valproate acid-induced cholestatic DILI mouse models, which reveal the great potential for effective cholestatic DILI management.