Rational Design of Hydrogel Polymer Nanoparticles Based on a Receptor Recognition Mechanism of Endotoxin and Its Application in Endotoxin Removal

Endotoxins, also known as lipopolysaccharides (LPS), are common exogenous pyrogens with notable pathogenic properties. The removal of endotoxins from water is essential due to the potential health hazards posed by exposure to bacterial or cyanobacterial endotoxins. Herein, we report an abiotic affinity material, a hydrogel polymer nanoparticle (HNP) as a potential absorbent for endotoxin removal. The polymer affinity ligand was discovered via a combination of rational design and directed evolution. Under the guidance of an endotoxin–receptor recognition mechanism, several receptor-like hydrogel polymer nanoparticle libraries were rationally created by incorporating candidate monomers with functionalities complementary either to the negatively charged phosphate groups or the hydrophobic fatty acid chains in endotoxin structure. MArg-HNP 4 that has high affinity, rapid kinetics, pH-responsivity, and broad-spectrum selectivity to LPS derivatives was identified by directed evolution, namely, multiple rounds of library construction and affinity screening. The screened MArg-HNP 4 was then in situ polymerized on the surface of SiO2 to prepare adsorption columns for the removal of endotoxin from water. The homemade column has LPS removal efficacy comparable to that packed with commercial ToxinEraser resin modified with polymyxin B. It also exhibits excellent regeneration performance, favorable biological safety, high cost-effectiveness, facile chemical synthesis, and high stability and robustness. These attributes make SiO2@MArg-HNP 4 a promising alternative to existing commercial endotoxin removal columns.