Galactose Glycopolymer-<i>Grafted</i> Silica\nNanoparticles: Synthesis and Binding Studies with Lectin

Weak binding of carbohydrates with protein receptors\npossesses\nserious drawbacks in the advancement of therapeutics; however, the\ndevelopment of strategies for multipoint interactions between carbohydrates\nand protein can overcome these challenges. One such method is developed\nin this work where glycopolymer-<i>grafted</i> silica nanoparticles\nwith a large number of carbohydrate units are prepared for the interactions\nwith multiple binding sites of the protein. First, a glycomonomer,\nβ-d-galactose-hydroxyethyl methacrylate (β-GEMA),\nwas synthesized in a two-step process by coupling β-d-galactose pentaacetate and hydroxyethyl methacrylate (HEMA), followed\nby deacetylation for the preparation of poly(β-GEMA) glycopolymers\n(GPs). Further, the poly(β-GEMA) chains were grafted onto the\nsilica nanoparticle (SiNP) surface by utilizing the “<i>grafting</i>-<i>from</i>” strategy of surface-initiated\nreversible addition-fragmentation chain transfer (RAFT) polymerization\nto prepare p(β-GEMA)-grafted SiNPs (GNPs). Five different chain\nlengths ranging from 10 to 40 kDa of the GPs and the GNPs were prepared,\nand various characterization techniques confirmed the formation of\nGPs and grafting of the GPs on the SiNP surface. The particle size\nof GNPs and the number of GPs grafted on the SiNP surface showed a\nstrong dependence on the chain length of the GPs. Further, the GNPs\nwere subjected to a binding study with β-galactose-specific\nprotein peanut agglutinin (PNA). A much stronger binding in the case\nof GNPs was observed with an association constant ∼320 times\nand ∼53 times than that of the monomeric methyl-β-d-galactopyranoside and the GPs, respectively. Additionally,\nthe binding of the PNA with GNPs and GPs was also studied with varying\nchain lengths to understand the effects of the chain length on the\nbinding affinity. A clear increase in binding constants was observed\nin the case of GNPs with increasing chain length of grafted GPs, attributed\nto the enhanced enthalpic and entropic contributions. This work holds\nits uniqueness in these improved interactions between carbohydrates\nand proteins, which can be used for carbohydrate-based targeted therapeutics.