Viscoelastic Janus Nanohydrogels for IL-1β Binding: Synthesis, Structure, and Release Kinetics

Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine central to the pathogenesis of numerous autoinflammatory and chronic inflammatory diseases. Current systemic anti-IL-1β therapies, while effective, are associated with significant side effects, necessitating the development of materials for localized immunomodulation. This study reports the design, synthesis, and comprehensive characterization of a novel, dual-function Viscoelastic Janus Nanohydrogel (VJNH) platform for the simultaneous sequestration of IL-1β and controlled release of an anti-inflammatory therapeutic. VJNHs were synthesized with an asymmetric Au@SiO₂ inorganic core; the gold (Au) face was functionalized with a high-affinity DNA aptamer for IL-1β capture, while the silica (SiO₂) face served as an anchor for a viscoelastic hydrogel shell. This shell was formed via dynamic Schiff base (C=N) chemistry between aldehyde-functionalized hyaluronic acid (oHA) and amine-rich gelatin. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) confirmed the asymmetric Janus morphology and spatially segregated surface chemistry. Rheological analysis demonstrated the ECM-mimetic viscoelastic properties of the network, including high solid-like character (G' > G'') and rapid stress relaxation (relaxation time τ ≈ 120 s), attributed to the dynamic covalent linkages. A comparative study identified an optimal VJNH-2 (1:1 oHA:Gelatin) formulation, which exhibited superior IL-1β binding capacity (≈ 180 ng/mg). Surface plasmon resonance (SPR) analysis revealed high-affinity and specific binding, with an equilibrium dissociation constant (Kₙ) of 1.24 nM. Concurrently, the VJNHs demonstrated sustained, pH-responsive release of a model drug (Dexamethasone), fitting a Fickian diffusion mechanism (Higuchi and Korsmeyer-Peppas models). All VJNH formulations were non-cytotoxic to L929 fibroblasts. These results establish VJNHs as a sophisticated "sense-and-respond" platform, synergizing spatial, mechanical, and chemical functionalities for advanced, localized treatment of inflammatory disorders.