Academician Yan Xiyun and Researcher Fan Kelong's team from the Institute of Biophysics, Chinese Academy of Sciences, have made a breakthrough in the research of tumor catalytic therapy using neutrophil-mimicking enzyme cascade catalysis. Their related paper was published on February 22nd in Nature Communications.
Nanozymes are a novel class of catalysts that can catalyze enzyme substrates under physiological or extreme conditions, serving as alternatives to natural enzymes for human health. In tumor therapy, the strategy of nanozyme-catalyzed hydrogen peroxide (H2O2) to generate reactive oxygen species for tumor cell killing has great potential. However, the low concentration of H2O2 (below 0.1 mM) in the tumor microenvironment limits its therapeutic effectiveness. The neutrophil enzyme cascade killing mechanism provides a new approach to overcome this problem, but currently, there are few reports of nanozymes with MPO-like activity.
Researchers simulated the principle of neutrophil enzyme cascade killing tumors and developed a nanozyme with both SOD-like and MPO-like activities. They found that Au1Pd3 alloy nanozymes could simulate the SOD-MPO cascade killing effect of neutrophils, causing DNA damage and cell apoptosis by producing HClO and 1O2. This significantly inhibited the growth of tumors in mouse models of colon cancer CT26 and breast cancer 4T1, and notably prolonged the survival of tumor-bearing mice. Additionally, Au1Pd3 alloy nanozymes exhibited good in vivo safety, mainly due to their catalytic substrate O2·- being more concentrated in tumor cells than in normal cells, making their cytotoxicity tumor-specific. Moreover, the ultra-small size of these nanozymes (less than 6 nanometers) endowed them with renal clearance function, avoiding long-term accumulation of nanozymes in the body.
This study of simulating neutrophil multi-enzyme cascade reactions for tumor therapy using biomimetic strategies will promote the development of more biomimetic treatment methods for antibacterial, tumor, or other diseases. The idea of using multi-enzyme activity nanozymes to mimic various natural enzyme-containing bodies will also promote research on nanozyme-mimicking organelles (such as lysosomes, peroxisomes, etc.), with the future possibility of creating nanozyme artificial organelles, and even nanozyme artificial cells. Additionally, the MPO-like activity possessed by nanozymes in this study is a novel type of nanozyme catalysis, which is still relatively scarce in current research. Given its potential applications in tumor therapy, antibacterial, and other fields, as well as the elucidation of its catalytic mechanism in this study, it will facilitate the discovery and design of more nanozymes with MPO-like activity.
Link to the paper: https://doi.org/10.1038/s41467-024-45668-3
