Targeting Extracellular Vesicles to the Arthritic Joint using a Damaged Cartilage Specific Antibody

Article


Topping, L. M., Thomas, B. L., Rhys, H. I., Tremoleda, J. L., Foster, M., Seed, M., Voisin, M., Vinci, C., Law, H. L., Perretti, M., Norling, L. V., Azevedo, H. S. and Nissim, A. 2020. Targeting Extracellular Vesicles to the Arthritic Joint using a Damaged Cartilage Specific Antibody. Frontiers in Immunology. 11 (Art. 10). https://doi.org/10.3389/fimmu.2020.00010
AuthorsTopping, L. M., Thomas, B. L., Rhys, H. I., Tremoleda, J. L., Foster, M., Seed, M., Voisin, M., Vinci, C., Law, H. L., Perretti, M., Norling, L. V., Azevedo, H. S. and Nissim, A.
Abstract

The targeted delivery of therapies to diseased tissues offers a safe opportunity to achieve optimal efficacy whilst limiting systemic exposure. These considerations apply to many disease indications, but are especially relevant for rheumatoid arthritis (RA), as RA is a systemic autoimmune disease which affects multiple joints. We have identified an antibody that is specific to damaged arthritic cartilage (anti-ROS-CII) that can be used to deliver treatments specifically to arthritic joints, yielding augmented efficacy in experimental arthritis. In the current study, we demonstrate that scaffold enriched with bioactive payloads can be delivered precisely to an inflamed joint and achieve superior efficacy outcomes consistent with the pharmacological properties of these payloads. As a scaffold, we have used extracellular vesicles (EV) prepared from human neutrophils (PMN), which possess intrinsic anti-inflammatory properties and the ability to penetrate inflamed arthritic cartilage.

EV fortified with anti-ROS-CII (EV/anti-ROS-CII) retained anti-ROS-CII specificity and bound exclusively to the damaged cartilage. Following systemic administration EV/anti-ROS-CII: a) exhibited the ability to localise specifically in the arthritic joint in vivo and b) was able to specifically target single (viral IL-10 or anti-TNF) or combined (viral IL-10 and anti-TNF) anti-inflammatory treatments to the arthritic joint, which accelerated attenuation of clinical and synovial inflammation.

Overall, this study demonstrates the attainability of targeting a pro-resolving biological scaffold to the arthritic joint. The potential of targeting scaffolds such as EV, nanoparticles or combination thereof alongside combined therapeutics is paramount for designing systemically administered broad-spectrum of anti-inflammatory treatments.

JournalFrontiers in Immunology
Journal citation11 (Art. 10)
ISSN1664-3224
Year2020
PublisherFrontiers Media
Publisher's version
License
File Access Level
Anyone
Supplemental file
File Access Level
Anyone
Digital Object Identifier (DOI)https://doi.org/10.3389/fimmu.2020.00010
Web address (URL)https://doi.org/10.3389/fimmu.2020.00010
Publication dates
Online14 Feb 2020
Publication process dates
Accepted06 Jan 2020
Deposited14 Feb 2020
Copyright holder© 2020 The Authors
Permalink -

https://repository.uel.ac.uk/item/876z6

Download files


Publisher's version
fimmu-11-00010.pdf
License: CC BY 4.0
File access level: Anyone


Supplemental file
  • 169
    total views
  • 167
    total downloads
  • 6
    views this month
  • 3
    downloads this month

Export as

Related outputs

Effects of heparan sulfates with different structures on leukaemia cells: U937 and THP-1 cell differentiation
Bajwa, P., Garrido Mesa, N., Seed, M. and Ayoub, S. 2019. Effects of heparan sulfates with different structures on leukaemia cells: U937 and THP-1 cell differentiation. 14th World Congress on Inflammation 2019. Sydney, AU 15 - 19 Sep 2019 World Congress on Inflammation.
Sucrose octasulphate regulates the expression of M1 and M2 macrophage-specific markers in U937 monocytes
Bajwa, P., Garrido Mesa, N., Seed, M. and Ayoub, S. 2019. Sucrose octasulphate regulates the expression of M1 and M2 macrophage-specific markers in U937 monocytes. 14th World Congress on Inflammation 2019. Sydney, AU 15 - 19 Sep 2019 World Congress on Inflammation.
Affective and enjoyment responses to 12 weeks of high intensity interval training and moderate continuous training in adults with Crohn’s disease
Bottoms, L., Leighton, D., Carpenter, R., Anderson, S., Langmead, L., Ramage, J., Faulkner, J., Coleman, E., Fairhurst, C., Seed, M. and Tew, G. 2019. Affective and enjoyment responses to 12 weeks of high intensity interval training and moderate continuous training in adults with Crohn’s disease. PLoS ONE. 14 (Art. e0222060). https://doi.org/10.1371/journal.pone.0222060
High-intensity interval training and moderate-intensity continuous training in adults with Crohn’s disease: a pilot randomised controlled trial
Tew, Garry A., Leighton, Dean, Carpenter, R., Anderson, Simon, Langmead, Louise, Ramage, John, Faulkner, James, Coleman, Elizabeth, Fairhurst, Caroline, Seed, M. and Bottoms, Lindsay 2019. High-intensity interval training and moderate-intensity continuous training in adults with Crohn’s disease: a pilot randomised controlled trial. BMC Gastroenterology. 19, p. Art. 19. https://doi.org/10.1186/s12876-019-0936-x
Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways
Piovezan, Anna P., Batisti, Ana P., Benevides, Maria L.A.C.S., Turnes, Bruna L., Martins, Daniel F., Kanis, Luiz, Duarte, Elisa C.W., Cavalheiro, Alberto J., Bueno, Paula C.P., Seed, M., Norling, Lucy V., Cooper, Dianne, Headland, Sarah, Souza, Patrícia R.P.S. and Perretti, Mauro 2017. Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways. Journal of Ethnopharmacology. 204, pp. 179-188. https://doi.org/10.1016/j.jep.2017.03.059
Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn’s disease: study protocol for a randomised controlled trial
Tew, Garry A., Carpenter, R., Seed, M., Anderson, Simon, Langmead, Louise, Fairhurst, Caroline and Bottoms, Lindsay 2017. Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn’s disease: study protocol for a randomised controlled trial. Pilot and Feasibility Studies. 2017 (3:17). https://doi.org/10.1186/s40814-017-0133-z
Applying refinement to the use of mice and rats in rheumatoid arthritis research
Hawkins, Penny, Armstrong, Rachel, Boden, Tania, Garside, Paul, Knight, Katherine, Lilley, Elliot, Seed, M., Wilkinson, Michael and Williams, Richard O. 2015. Applying refinement to the use of mice and rats in rheumatoid arthritis research. Inflammopharmacology. 23 (4), pp. 131-150.
Does this case hold the answer to one of the worse types of pain in medicine--that of loin pain haematuria syndrome (LPHS)
Russell, Alan, Chatterjee, Suman and Seed, M. 2015. Does this case hold the answer to one of the worse types of pain in medicine--that of loin pain haematuria syndrome (LPHS). BMJ Case Reports. 2015 (apr26). https://doi.org/10.1136/bcr-2014-209165
Animal models of rheumatoid arthritis: How informative are they?
McNamee, Kay, Williams, Richard and Seed, M. 2015. Animal models of rheumatoid arthritis: How informative are they? European Journal of Pharmacology. 759, pp. 278-286.
Targeting of viral interleukin-10 with an antibody fragment specific to damaged arthritic cartilage improves its therapeutic potency
Hughes, Chris, Sette, Angelica, Seed, M., D’Acquisto, Fulvio, Manzo, Antonio, Vincent, Tonia L, Lim, Ngee and Nissim, Ahuva 2014. Targeting of viral interleukin-10 with an antibody fragment specific to damaged arthritic cartilage improves its therapeutic potency. Arthritis Research & Therapy. 16 (4), p. R151.