Intracellular Delivery of Itaconate by Metal–Organic Framework-Anchored Hydrogel Microspheres for Osteoarthritis Therapy

Abstract

Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously hamper the clinical translation. Herein, IA-encapsulated zeolitic imidazolate framework-8 (IA-ZIF-8) nanoparticles were self-assembled by zinc ions, 2-methylimidazole, and IA to render them pH-responsive. Subsequently, IA-ZIF-8 nanoparticles were firmly immobilized in hydrogel microspheres via one-step microfluidic technology. It was demonstrated in vitro experiments that IA-ZIF-8-loaded hydrogel microspheres (IA-ZIF-8@HMs) exhibited good anti-inflammatory and anti-oxidative stress effects by releasing pH-responsive nanoparticles into chondrocytes. Importantly, compared with IA-ZIF-8, IA-ZIF-8@HMs showed better performance in the treatment of OA due to their superior performance in sustained release. Thus, such hydrogel microspheres not only hold enormous potential for OA therapy, but also provide a novel avenue for cell-impermeable drugs by constructing appropriate drug delivery systems.

Unveiling the versatility of gelatin methacryloyl hydrogels: a comprehensive journey into biomedical applications

“…Itaconate-encapsulated ZIF-8 NPs immobilized in GelMA [159], Curcumin-incorporated GelMA [160], Methacrylated chondroitin sulfate/ methacrylated HA/GelMA [161]. Adipose-derived stromal/stem cells-incorporated GelMA/MAAmodified poly(amidoamine) [162], GelMA/ engineered cartilage gel [163], Diclofenac sodium-incorporated GelMA/acrylamide/2methacryloyloxyethyl phosphorylcholine [97], bMSCs affinity peptide sequence PFSSTKT-modified chondrocyte ECM particles/GelMA [164], Nanoclay/alginate/GelMA [165], Denatured collagen/Gel-MA/Laponite [166], Iron oxide NPs/GelMA [167], Alanyl-Glutamine-modified GelMA [168] are some of the recent studies that demonstrated favorable results in cartilage tissue repair.…”

Nano‐Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications

“…A similar nano-micro combination strategy was also reported in the study by Yu et al on self-assembled hydrogel microspheres containing zinc ion nanoparticles. [309] Moreover, in the research by Shen et al, they used electrostatic self-assembly to coat the surface of manganese dioxide nanoparticles with a layer of chitosan, modifying the nanoparticles with active groups (amino groups). [310] With the presence of amino groups, these nanoparticles can form chemical bonds with the hydrogel matrix through condensation reactions, thereby being firmly loaded onto the hydrogel microspheres and used for the treatment of Intervertebral disc degeneration (IVDD).…”

Enhanced Surface Immunomodification of Engineered Hydrogel Materials through Chondrocyte Modulation for the Treatment of Osteoarthritis

“…Natural hydrogels include collagen, gelatin, chitosan, fibrin, and alginate. Natural hydrogels are known for their biocompatibility and biodegradability, making them suitable for modified intra-articular drug delivery [47]. Synthetic hydrogels include polyvinyl alcohol, polyethylene glycol, and polycaprolactone.…”