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PloS one2017; 12(12); e0190216; doi: 10.1371/journal.pone.0190216

Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model.

Abstract: Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE2 were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function, which could potentially lead to a new diagnostic technique for early detection of cartilage disease.
Publication Date: 2017-12-29 PubMed ID: 29287105PubMed Central: PMC5747449DOI: 10.1371/journal.pone.0190216Google Scholar: Lookup
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  • Journal Article
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Summary

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The research investigated the potential use of superparamagnetic iron oxide nanoparticles (SPIONs) in magnetic resonance imaging (MRI) to visualize cartilage changes in a large animal model. The results suggested that using SPIONs could provide an effective imaging technique to identify early signs of cartilage disease, although nanoparticles triggered a dose-dependent inflammatory response that warrants further investigation.

Overview of the Study

The study presents a proof of concept regarding the use of nanoparticles to assess the state of the cartilage barrier in a large animal model, specifically a porcine metacarpophalangeal cartilage model. The researchers used nanoparticles to enhance diagnostic imaging via MRI. The approach involved testing the permeation of two sizes of fluorophore-conjugated gold nanoparticles (30nm and 80nm) through conditioned and unconditioned cartilage. The procedures included multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement.

The study further involved conducting MRI scans before and after injecting SPIONs into the joints to assess changes in signal due to particle permeation. The effect of matrix depletion, the loss of extracellular matrix components that is a significant aspect of cartilage disease, was also evaluated.

Findings of the Study

The findings indicated an increase in MRI signal following the conditioning of the porcine joints treated with SPIONs. This suggests that the use of nanoparticles could provide an effective method for imaging the composition of cartilage.
The study also evaluated the potential pro-inflammatory effects of delivering nanoparticles into the joints. By exposing co-cultures of equine synovium and cartilage tissue to increasing doses of SPIONs, researchers observed dose-dependent inflammatory responses. Assessments of IL-6, IL-10, IFN-γ and PGE2 in culture media and neutrophil migration assays were conducted to review this response.

Significance of the Study

The study provides promising preliminary data on the utility of SPIONs to create an imaging contrast for MRI studies of the cartilage. The findings also highlighted potential inflammatory responses to intra-articular nanoparticle delivery, an important consideration for future studies and potential clinical applications.

The researchers believe this to be the first report of using SPIONs as an intra-articular contrast agent for MRI. The findings suggest that this approach could provide a novel diagnostic method for the early detection of cartilage disease, potentially helping to reduce patient morbidity by enabling more timely interventions.

Cite This Article

APA
Labens R, Daniel C, Hall S, Xia XR, Schwarz T. (2017). Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model. PLoS One, 12(12), e0190216. https://doi.org/10.1371/journal.pone.0190216

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 12
Issue: 12
Pages: e0190216
PII: e0190216

Researcher Affiliations

Labens, Raphael
  • School of Animal and Veterinary Sciences, Faculty of Science, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
Daniel, Carola
  • The Roslin Institute, Easter Bush Campus, The University of Edinburgh, Midlothian, United Kingdom.
Hall, Sarah
  • Animal & Veterinary Sciences, Scotland's Rural College, Easter Bush Campus, Midlothian, United Kingdom.
Xia, Xin-Rui
  • Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, United States of America.
Schwarz, Tobias
  • Royal (Dick) School of Veterinary Studies, Easter Bush Campus, The University of Edinburgh, Midlothian, United Kingdom.

MeSH Terms

  • Animals
  • Biomarkers / metabolism
  • Cartilage, Articular / diagnostic imaging
  • Cartilage, Articular / metabolism
  • Chemotaxis, Leukocyte
  • Coculture Techniques
  • Drug Administration Routes
  • Female
  • Fluorescent Dyes
  • Horses
  • Joints
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles / administration & dosage
  • Male
  • Microscopy, Confocal
  • Models, Animal
  • Neutrophils / cytology
  • Swine

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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