Sepsis is a critical condition with high morbidity, high mortality and high cost of treatment in ICUs, causing more than 11 million deaths worldwide each year. Blood purification strategies based on endotoxin clearance have important clinical significance in the treatment of sepsis. Recently, the team of Qing Guangyan, a researcher at the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, developed an ultra-precise endotoxin separation material. Through the “tailor-made” material design concept, the team proposed a strategy based on phage display screening and hemocompatible pitidyl polymer design, which realized the in-situ, rapid and accurate removal of specific endotoxins in the blood. The results were published in Advanced Materials.
Schematic diagram of blood endotoxin separation material. Photo courtesy of Dalian Chemical Properties
Currently, the structural complexity of endotoxins, the complexity of blood components, and the low abundance of endotoxins in the blood make it challenging to clear specific endotoxins from the blood.
In this work, the team used Escherichia coli endotoxin as a model and discovered an endotoxin affinity peptide with high affinity, high specificity and high detoxification activity for the target endotoxin through iterative affinity screening and endotoxin detoxification activity screening on phage surface display. The peptide can not only accurately distinguish endotoxins from other blood components, but also accurately identify and clear specific endotoxin molecules. The peptide-based polymer designed in this way can reduce the endotoxin level in the blood of sepsis rabbits from 2.63±0.01 to 0.78±0.05 EU/mL with a clearance rate greater than 70%, significantly alleviating endotoxin-induced multi-organ damage and sepsis prognosis.
This work provides a general example for the development of ultra-precise endotoxin separation materials, which is expected to create a library of highly selective adsorption materials with full coverage of endotoxin series molecules, thereby comprehensively improving the selectivity of blood purification materials for endotoxin removal, and realizing accurate identification and removal of specific endotoxin molecules.
In addition, this top-down ligand screening strategy is also suitable for the specific clearance of other endogenous and exogenous hemotoxins, which is conducive to promoting the exploration and application of “personalized” precision medicine in the field of global critical blood purification. (Source: Sun Danning, China Science News)
Related paper information:https://doi.org/10.1002/adma.202302560