Inside-Out Oriented Choline Phosphate-Based Biomimetic Magnetic Nanomaterials for Precise Recognition and Analysis of C-Reactive Protein

Abstract

Phospholipid-based materials exhibit great application potential in the fields of chemistry, biology, and pharmaceutical sciences. In this study, an inside-out oriented choline phosphate molecule, 2-{2-(methacryloyloxy)ethyldimethylammonium}ethyl n-butyl phosphate (MBP), was proposed and verified as a novel ligand of C-reactive protein (CRP) to enrich the functionality of these materials. Compared with phosphorylcholine (PC)-CRP interactions, the binding between MBP and CRP was not affected by the reverse position of phosphate and choline groups and even found more abundant binding sites. Thus, high-density MBP-grafted biomimetic magnetic nanomaterials (MBP-MNPs) were fabricated by reversible addition-fragmentation chain transfer polymerization based on thiol-ene click chemistry. The novel materials exhibited multifunctional applications for CRP including purification and ultrasensitive detection. On the one hand, higher specificity, recovery (90%), purity (95%), and static binding capacity (198.14 mg/g) for CRP were achieved on the novel materials in comparison with traditional PC-based materials, and the enriched CRP from patient serum can maintain its structural integrity and bioactivity. On the other hand, the CRP detection method combining G-quadruplex and thioflavin T developed with MBP-MNPs showed a lower detection limit (10 pM) and wider linear range (0.1-50 nM) than most PC-functionalized analytical platforms. Therefore, the inside-out oriented choline phosphate can not only precisely recognize CRP but also be combined with biomimetic nanomaterials to provide high application potential.