Rational Design of\nHydrogel Polymer Nanoparticles\nBased on a Receptor Recognition Mechanism of Endotoxin and Its Application\nin Endotoxin Removal

Endotoxins,\nalso known as lipopolysaccharides (LPS),\nare common\nexogenous pyrogens with notable pathogenic properties. The removal\nof endotoxins from water is essential due to the potential health\nhazards posed by exposure to bacterial or cyanobacterial endotoxins.\nHerein, we report an abiotic affinity material, a hydrogel polymer\nnanoparticle (HNP) as a potential absorbent for endotoxin removal.\nThe polymer affinity ligand was discovered via a combination of rational\ndesign and directed evolution. Under the guidance of an endotoxin–receptor\nrecognition mechanism, several receptor-like hydrogel polymer nanoparticle\nlibraries were rationally created by incorporating candidate monomers\nwith functionalities complementary either to the negatively charged\nphosphate groups or the hydrophobic fatty acid chains in endotoxin\nstructure. <b>MArg-HNP 4</b> that has high affinity, rapid kinetics,\npH-responsivity, and broad-spectrum selectivity to LPS derivatives\nwas identified by directed evolution, namely, multiple rounds of library\nconstruction and affinity screening. The screened <b>MArg-HNP 4</b> was then <i>in situ</i> polymerized on the surface of\nSiO<sub>2</sub> to prepare adsorption columns for the removal of endotoxin\nfrom water. The homemade column has LPS removal efficacy comparable\nto that packed with commercial ToxinEraser resin modified with polymyxin\nB. It also exhibits excellent regeneration performance, favorable\nbiological safety, high cost-effectiveness, facile chemical synthesis,\nand high stability and robustness. These attributes make <b>SiO</b><sub><b>2</b></sub><b>@MArg-HNP 4</b> a promising alternative\nto existing commercial endotoxin removal columns.