Academician Yan Xiyun and his team at the Institute of Biophysics, Chinese Academy of Sciences, along with researcher Fan Kelong, have made significant progress in the research of nanoenzyme-simulated neutrophil multienzyme cascade catalytic therapy for tumors. The relevant paper was published on February 22nd in "Nature Communications."
Nanoenzymes are a novel class of catalysts capable of catalyzing enzyme substrates under physiological or extreme temperature conditions, serving as natural enzyme substitutes for human health. In the realm of tumor treatment, the strategy of nanoenzyme catalysis of hydrogen peroxide (H2O2) to generate reactive oxygen species for tumor cell destruction holds immense potential. However, the low concentration of H2O2 in the tumor microenvironment (below 0.1 mM) hampers its therapeutic effectiveness. The multienzyme cascade killing mechanism of neutrophils offers a breakthrough for this issue, but currently, there are few reported nanoenzymes with myeloperoxidase (MPO) activity.
Researchers simulated the neutrophil enzyme-catalyzed cascade killing of tumors and developed a nanoenzyme simultaneously exhibiting superoxide dismutase (SOD) and MPO-like activities. The study revealed that Au1Pd3 alloy nanoenzyme can simulate the SOD-MPO cascade killing effect of neutrophils. By generating HClO and 1O2, it induces DNA damage and cell apoptosis. This nanoenzyme significantly inhibits tumor growth in both mouse colon cancer CT26 and breast cancer 4T1 xenograft models, markedly prolonging the survival of tumor-bearing mice. Additionally, the Au1Pd3 alloy nanoenzyme exhibits excellent in vivo safety, primarily due to its catalysis of substrate O2·- at concentrations higher in tumor cells than in normal cells, giving it tumor-specific cytotoxicity. Furthermore, the nanoenzyme's ultra-small size (less than 6 nanometers) endows it with renal clearance functionality, preventing long-term accumulation in the body.
This study, simulating the biomimetic strategy of neutrophil multienzyme cascade reactions for tumor therapy, will drive the development of more biomimetic treatment approaches for antimicrobial, tumor, or other diseases. The concept of using multi-enzyme activity nanoenzymes to simulate various natural enzyme-containing organelles will also advance research in nanoenzyme-simulated organelles, such as lysosomes and peroxisomes. In the future, this could lead to the creation of nanoenzyme artificial organelles and even nanoenzyme artificial cells. Moreover, the MPO-like activity exhibited by the nanoenzyme in this study represents a novel catalytic type of nanoenzyme, which is currently underexplored. Given its potential applications in tumor treatment and antimicrobial fields, coupled with the elucidation of its catalytic mechanism in this research, it will likely spur the discovery and design of more MPO-like activity nanoenzymes.
For more information, refer to the paper: https://doi.org/10.1038/s41467-024-45668-3
