Multivalent boronolectin nanoparticles modulate monocyte migration via sialic acid shielding in osteoarthritis

Recruitment of circulating monocytes into the joint space drives low-grade inflammation, characteristic of diseases such as osteoarthritis (OA). During extravasation, monocytes transiently upregulate sialic acids (Sia), providing a dynamic molecular cue that can be exploited for selective immune-cell targeting. Here, we designed a multivalent Sia-binding nanoparticle (NP) by conjugating phenylboronic acid (PBA) to polyethyleneimine (PEI) and assembling this amphiphilic targeting polymer onto a biodegradable poly(D,L-lactide-co-glycolide) (PLGA) core via nanoprecipitation, yielding PBA-PEI@PLGA. Integration of dynamic covalent PBA-Sia interactions with PEI-mediated electrostatic attraction, enhances avidity relative to single-modality PBA targeting. Comprehensive characterization confirmed Sia-selective binding and pH-sensitivity of the polymer, consistent with enhanced PBA-Sia interactions under acidic conditions. The colloidally stable, ~240 nm NP was biocompatible in cell lines and primary human blood monocytes. Importantly, biological Sia-selectivity was retained under physiological flow conditions mimicking circulation, supporting the translational relevance of the targeting mechanism. Functionally, NPs reduced monocyte migration towards monocyte chemoattractant protein-1 (MCP-1), and critically, attenuated migration toward OA synovial fluid, demonstrating a direct impact on clinically relevant inflammatory cues. These findings demonstrate that PBA-PEI@PLGA act as a modular immunoregulatory platform that selectively engages Sia on activated monocytes and dampens Sia-mediated recruitment processes, highlighting its potential for targeting monocyte-driven inflammation in OA.