Journal article
Targeting extracellular vesicles to the arthritic joint using a damaged cartilage specific antibody
- Abstract:
- The targeted delivery of therapies to diseased tissues offers a safe opportunity to achieve optimal efficacy while 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 scaffolds 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 (EVs) prepared from human neutrophils (PMNs), 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 localize 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 a combination thereof alongside combined therapeutics is paramount for designing systemically administered broad-spectrum of anti-inflammatory treatments.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.9MB, Terms of use)
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- Publisher copy:
- 10.3389/fimmu.2020.00010
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 11
- Article number:
- 10
- Publication date:
- 2020-02-14
- Acceptance date:
- 2020-01-06
- DOI:
- EISSN:
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1664-3224
- Language:
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English
- Keywords:
- Pubs id:
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pubs:1080863
- UUID:
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uuid:4c445c0c-7305-4e73-a2ea-e79d1461997c
- Local pid:
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pubs:1080863
- Source identifiers:
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1080863
- Deposit date:
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2020-01-06
Terms of use
- Copyright holder:
- Topping et al.
- Copyright date:
- 2020
- Rights statement:
- Copyright © 2020 Topping, Thomas, Rhys, Tremoleda, Foster, Seed, Voisin, Vinci, Law, Perretti, Norling, Azevedo and Nissim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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