Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis
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Abstract
BACKGROUND: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration, serious adverse reactions during long-term administration. To achieve better treatment, 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 biodistribution 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.
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Engineered exosomes modified with folic acid, PEG, and cholesterol loaded with dexamethasone sodium phosphate better protected bone and cartilage in CIA mice and reduced joint inflammation without obvious liver toxicity.
“In vivo biodistribution experiments showed that these engineered exosomes better protected bone and cartilage in CIA mice and reduced joint inflammation without obvious liver toxicity.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [82]
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- Authors
- Yan, F., Zhong, Z., Wang, Y., Feng, Y., Mei, Z., Li, H., Chen, X., Cai, L., & Li, C.
- Affiliations
- Southwest Medical University (CN)
- Affiliated Hospital of Southwest Medical University (CN)
- Sichuan University (CN)
- Corresponding author
- Cai, Liang
- Li, Chunhong
- Venue
- Journal of Nanobiotechnology
- Published
- 2020-08-20
- Volume
- 18
- Issue
- 1
- Pages
- 115-115
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC7441703
- OpenAlex
- W3050111167
- Cited by
- 197
- References
- 54
- Citations by year
- 2026: 18 · 2025: 36 · 2024: 43 · 2023: 36 · 2022: 39 · 2021: 24 · 2020: 1
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Major Science and Technology Projects of China (81803478)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- rheumatoid arthritis, exosomes, biomimetic nanoparticles, dexamethasone, glucocorticoids, targeted drug delivery, folic acid, joint inflammation, anti-inflammatory cytokines, collagen-induced arthritis, tissue distribution, biocompatibility, nanocarriers
- MeSH terms
- RAW 264.7 Cells, Animals, Anti-Inflammatory Agents, Arthritis, Rheumatoid, Cholesterol, Dexamethasone, Folic Acid, Joints, Male, Polyethylene Glycols, Biomimetic Materials, Mice, Nanoparticles, Exosomes
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