Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

Abstract

Backgroud: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo pharmacodynamic experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. Conclusion The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

“…Yan et al reported a platform of RAW 264.7-derived EVs coupled with FA-bearing polyethylene glycol (PEG)-cholesterol (Chol) to encapsulate and control the delivery of dexamethasone (Dex), which is the most frequently used glucocorticoids to treat RA in the clinic. Dex can downregulate pro-inflammatory cytokines of macrophages 183 . The incorporation of Dex into EVs was achieved by electroporation.…”

Advancement of nanomedicines in chronic inflammatory disorders

“…They are very unstable when dissolved in water molecules; therefore, the product's shelf life is quite short. Inorganic nanoparticles are very unstable, have significant biological toxicity, and have a poor targeting impact (Yan et al 2020 ).…”

Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy

“…After staining the cell nuclei with DAPI, endocytosis was observed by confocal laser scanning microscopy (Leica Microsystems, Wetzlar, Germany) [37]. Uptake of the labeled formulations was also observed by ow cytometry using a Verse cytometer (BD Biosciences, Franklin Lakes, NJ, USA) after stimulating RAW264.7 cells for 24 h with LPS.…”

“…RA severity was evaluated by rating the paw swelling according to the following scale [37]: 0, no signs of swelling; 1, mild in ammation and swelling of individual toes; 2, moderate in ammation and swelling of all toes; 3, severe swelling of the entire paw; and 4, maximum swelling of the limb. The scores of each paw were summed to calculate the total arthritis index score for the animal.…”

“…The resulting drug delivery system (FPD/MV/MTX@ZIF-8) exhibited enhanced drug loading capacity, controlled drug release under acidic conditions, good biocompatibility, and prolonged time in circulation [36]. In our previous work, we achieved only 20% dexamethasone loading in exosomes [37], and the DLE was 3.49% for plasmid DNA encoding the anti-in ammatory cytokine interleukin-10 and 9.67% for betamethasone sodium phosphate into biomimetic vector M 2 exosomes[38], while we achieved much higher loading of 70% with FPD/MV/MTX@ZIF-8. B) and methanol were purchased from Kelong Chemical Reagent Factory (Chengdu, China).…”