Outperforming Biorecognition: Epitope-Imprinted Nanoparticle Enables High-Species-Specificity Purification of Human IgG

Abstract

Monoclonal antibodies are key therapeutics, but their purification remains costly and complex. Current industrial standards use biorecognition ligands such as protein A/G, which lack species-specificity. We report a highly species-selective nanoscale molecularly imprinted polymer (MIP) that enables the efficient purification of human IgG from complex samples, outperforming protein A/G in recognition performance. Unlike the “domain-to-domain” recognition for protein A/G, the “pocket-to-epitope” recognition mode endowed by our MIP enables precise differentiation of human IgG from IgGs of other species, which share a highly conserved structure. The MIP also exhibits “pit-one-against-four” performance, demonstrating high affinity toward all human IgG subclasses (with a K_d value at the nM level). Moreover, owing to its excellent stability, the MIP allows for long-term storage at ambient temperature. Therefore, this study not only provides a new promising affinity nanomaterial for efficient antibody purification but also showcases the unique strength of MIPs to outperform biorecognition in terms of species-specificity.