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Folate‐targeted nanoparticles show efficacy in the treatment of inflammatory arthritis
Open accessAbstract
Objective: To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA‐ and methotrexate (MTX)–conjugated dendrimer (G5‐FA‐MTX) as a therapeutic for the inflammatory disease of arthritis. Methods: In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence‐tagged G5‐FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen‐induced arthritis to evaluate the therapeutic potential of G5‐FA‐MTX. Results: Folate‐targeted dendrimer bound and internalized in a receptor‐specific manner into both folate receptor β–expressing macrophage cell lines and primary mouse macrophages. The conjugate G5‐FA‐MTX acted as a potent antiinflammatory agent and reduced arthritis‐induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease. Conclusion: The use of folate‐targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.
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Cited by
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Wong, P. T., & Choi, S. K. (2015) · Chemical Reviews · doi:10.1021/cr5004634 · Cited by 507
Yang, Y., Guo, L., Wang, Z., Liu, P., Liu, X., Ding, J., & Zhou, W. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120390 · Cited by 503
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Han, J., Kim, Y. S., Lim, M.-Y., Kim, H. Y., Kong, S., Kang, M., Choo, Y. W., Jun, J. H., Ryu, S., Jeong, H.-Y., et al. (2018) · ACS Nano · doi:10.1021/acsnano.7b09107 · Cited by 258
Metadata
- Authors
- Thomas, T. P., Goonewardena, S. N., Majoros, I. J., Kotlyar, A., Cao, Z., Leroueil, P. R., & Baker, J. R.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2011-08-31
- Volume
- 63
- Issue
- 9
- Pages
- 2671-2680
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W1996498972
- Cited by
- 208
- References
- 0
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- green
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- Thomas, T. P., Goonewardena, S. N., Majoros, I. J., Kotlyar, A., Cao, Z., Leroueil, P. R., & Baker, J. R. (2011). Folate‐targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis & Rheumatism. https://doi.org/10.1002/art.30459
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