A research team led by Prof. ZHANG Lijuan from the Shanghai Advanced Research Institute of the Chinese Academy of Sciences, and the collaborators from Tongji University, proposed a peptide-stabilized lactate oxidase and catalase system, which can effectively deliver oxygen to cells and tissues in nerve injury treatment. The findings were published in Cell Biomaterials.

Nanobubbles hold great potential in the field of biomedical gas delivery. Their extensive gas-liquid interface and relatively high internal pressure endow them with gas transport efficiency far superior to that of traditional methods.

In this study, the researchers investigated the formation, stabilization/diffusion processes and biological effects of enzyme-driven nanobubbles. They proposed that enzyme molecules could serve as ideal bioreactors for nanobubble fabrication as their locally high concentrations of gaseous molecules produced in efficient biocatalytic centers and hydrophobic regions within microdomain structures.

Inspired by enzyme complexes in metabolic processes, the researchers constructed a peptide-stabilized lactate oxidase/catalase (LOx/CAT@PNFs) system which utilized endogenous substances (lactate and hydrogen peroxide) in living organisms to generate oxygen nanobubbles via enzymatic reactions. They found that the hydrophobic microdomains in peptide nanofibers contributed to the stabilization of these nanobubbles.

“How to detect the formation, chemical identification and evolution of nanobubbles in this system is a big challenge. We have detected in-situ the nanobubbles generated by the LOx/CAT@PNFs system and oxygen inside through synchrotron radiation X-ray nanoscale imaging, and then explored their dynamics by using the liquid in-situ transmission electron microscopy,” said Prof. ZHANG, one corresponding author of the study.

By regulating lactate metabolism, improving local oxygen supply, and alleviating oxidative stress, the LOx/CAT@PNFs system effectively enhanced the neuronal survival and improved the neural function, and demonstrated excellent therapeutic efficacy in both acute and chronic neurotoxic encephalopathy models.

This work offers new insights into advancing the application of nanobubble gas delivery systems within biological organisms, and has implications for exploring enzyme-driven gas-mediated metabolic regulation mechanisms.