RAFT-Polymerized Thermoresponsive Glycopolymer-Grafted-Nanoparticles: Modulation of Lectin Binding.

Abstract

The ability of thermoresponsive glycopolymers to undergo solubility transitions at physiological temperatures can enable the modulation of carbohydrate-lectin interactions. This study examines the binding of thermoresponsive glycopolymer-grafted-silica nanoparticles to lectin concanavalin A at different temperatures. α-d-mannose-hydroxyethyl methacrylate (α-MEMA) and N-isopropylacrylamide (NIPAM) are graft-copolymerized onto silica nanoparticles (SiNPs) via RAFT polymerization to form p(MEMA-co-NIPAM)-grafted-SiNPs. Results show that the sequence and structural arrangement of glycopolymer chains strongly influence lectin binding, especially under temperature modulation. Chains extending outward from the SiNP core yielded strong binding, with an association constant of ∼8 × 10⁶ M^-1, which is ∼1200 times higher than that of monomeric methyl-α-d-mannopyranoside, due to greater carbohydrate accessibility to the lectin. In contrast, glycopolymer chains that are randomly arranged/closer to the core showed weak/no binding. The binding is further strengthened below the lower critical solution temperature due to increased polymer solubility, with additional enhancement at longer chain lengths. These observations represent an advancement in the design of functional materials for targeted therapy.