期刊
JOURNAL OF NANOBIOTECHNOLOGY
卷 20, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12951-022-01447-0
关键词
Rheumatoid arthritis; Metal-organic framework; Microvesicles; Folate receptor
资金
- National Natural Science Foundation of China [81803478]
- Science and Technology Project of Luzhou Government [2019-JYJ-51]
- Science and Technology Project of the Health Planning Committee of Sichuan [18ZD036]
- Special Support Project for Young Talents of Southwest Medical University
- Key Project of Application and Basic Research of Southwest Medical University [2021ZKZD016]
A novel anti-rheumatoid arthritis nanoparticle complex was designed and constructed in this study, which can improve targeted accumulation in inflamed joints and reduce side effects.
Background: Methotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects. Results: Here, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor beta for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (similar to 70%) and EE (similar to 82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications. Conclusions: This study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment.
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