FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Get Full Text
Publication Date: 2017-12-29 PubMed ID: 29287105PubMed Central: PMC5747449DOI: 10.1371/journal.pone.0190216Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

PloS one
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.

References

This article includes 49 references
  1. Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, Goldring SR, Jones G, Teichtahl AJ, Pelletier JP. Osteoarthritis.. Nat Rev Dis Primers 2016 Oct 13;2:16072.
    doi: 10.1038/nrdp.2016.72pubmed: 27734845google scholar: lookup
  2. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  3. Venn M, Maroudas A. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. Chemical composition.. Ann Rheum Dis 1977 Apr;36(2):121-9.
    pmc: PMC1006646pubmed: 856064doi: 10.1136/ard.36.2.121google scholar: lookup
  4. Maroudas A. Transport of solutes through cartilage: permeability to large molecules.. J Anat 1976 Nov;122(Pt 2):335-47.
    pmc: PMC1231906pubmed: 1002608
  5. Torzilli PA, Arduino JM, Gregory JD, Bansal M. Effect of proteoglycan removal on solute mobility in articular cartilage.. J Biomech 1997 Sep;30(9):895-902.
    pubmed: 9302612doi: 10.1016/s0021-9290(97)00059-6google scholar: lookup
  6. Guermazi A, Alizai H, Crema MD, Trattnig S, Regatte RR, Roemer FW. Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis.. Osteoarthritis Cartilage 2015 Oct;23(10):1639-53.
    doi: 10.1016/j.joca.2015.05.026pubmed: 26050864google scholar: lookup
  7. Lakin BA, Snyder BD, Grinstaff MW. Assessing Cartilage Biomechanical Properties: Techniques for Evaluating the Functional Performance of Cartilage in Health and Disease.. Annu Rev Biomed Eng 2017 Jun 21;19:27-55.
    doi: 10.1146/annurev-bioeng-071516-044525pubmed: 28226218google scholar: lookup
  8. van Tiel J, Siebelt M, Reijman M, Bos PK, Waarsing JH, Zuurmond AM, Nasserinejad K, van Osch GJ, Verhaar JA, Krestin GP, Weinans H, Oei EH. Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: correlation with ex-vivo reference standards.. Osteoarthritis Cartilage 2016 Jun;24(6):1012-20.
    doi: 10.1016/j.joca.2016.01.137pubmed: 26851449google scholar: lookup
  9. Freedman JD, Lusic H, Snyder BD, Grinstaff MW. Tantalum oxide nanoparticles for the imaging of articular cartilage using X-ray computed tomography: visualization of ex vivo/in vivo murine tibia and ex vivo human index finger cartilage.. Angew Chem Int Ed Engl 2014 Aug 4;53(32):8406-10.
    doi: 10.1002/anie.201404519pmc: PMC4303344pubmed: 24981730google scholar: lookup
  10. van Buul GM, Kotek G, Wielopolski PA, Farrell E, Bos PK, Weinans H, Grohnert AU, Jahr H, Verhaar JA, Krestin GP, van Osch GJ, Bernsen MR. Clinically translatable cell tracking and quantification by MRI in cartilage repair using superparamagnetic iron oxides.. PLoS One 2011 Feb 23;6(2):e17001.
    doi: 10.1371/journal.pone.0017001pmc: PMC3044153pubmed: 21373640google scholar: lookup
  11. Korchinski DJ, Taha M, Yang R, Nathoo N, Dunn JF. Iron Oxide as an MRI Contrast Agent for Cell Tracking.. Magn Reson Insights 2015;8(Suppl 1):15-29.
    doi: 10.4137/MRI.S23557pmc: PMC4597836pubmed: 26483609google scholar: lookup
  12. Wang YX. Superparamagnetic iron oxide based MRI contrast agents: Current status of clinical application.. Quant Imaging Med Surg 2011 Dec;1(1):35-40.
    doi: 10.3978/j.issn.2223-4292.2011.08.03pmc: PMC3496483pubmed: 23256052google scholar: lookup
  13. Reiner CS, Lutz AM, Tschirch F, Froehlich JM, Gaillard S, Marincek B, Weishaupt D. USPIO-enhanced magnetic resonance imaging of the knee in asymptomatic volunteers.. Eur Radiol 2009 Jul;19(7):1715-22.
    doi: 10.1007/s00330-009-1343-4pubmed: 19330333google scholar: lookup
  14. Simon GH, von Vopelius-Feldt J, Wendland MF, Fu Y, Piontek G, Schlegel J, Chen MH, Daldrup-Link HE. MRI of arthritis: comparison of ultrasmall superparamagnetic iron oxide vs. Gd-DTPA.. J Magn Reson Imaging 2006 May;23(5):720-7.
    doi: 10.1002/jmri.20556pubmed: 16557494google scholar: lookup
  15. Amirabadi A, Vidarsson L, Miller E, Sussman MS, Patil K, Gahunia H, Peel SA, Zhong A, Weiss R, Detzler G, Cheng HL, Moineddin R, Doria AS. USPIO-related T1 and T2 mapping MRI of cartilage in a rabbit model of blood-induced arthritis: a pilot study.. Haemophilia 2015 Jan;21(1):e59-69.
    doi: 10.1111/hae.12601pubmed: 25545305google scholar: lookup
  16. Patil US, Adireddy S, Jaiswal A, Mandava S, Lee BR, Chrisey DB. In Vitro/In Vivo Toxicity Evaluation and Quantification of Iron Oxide Nanoparticles.. Int J Mol Sci 2015 Oct 15;16(10):24417-50.
    doi: 10.3390/ijms161024417pmc: PMC4632758pubmed: 26501258google scholar: lookup
  17. Vermeij EA, Koenders MI, Bennink MB, Crowe LA, Maurizi L, Vallée JP, Hofmann H, van den Berg WB, van Lent PL, van de Loo FA. The in-vivo use of superparamagnetic iron oxide nanoparticles to detect inflammation elicits a cytokine response but does not aggravate experimental arthritis.. PLoS One 2015;10(5):e0126687.
    doi: 10.1371/journal.pone.0126687pmc: PMC4425489pubmed: 25955417google scholar: lookup
  18. Nigam S, Barick KC, Bahadur D. Development of citrate-stabilized Fe3O4 nanoparticles: Conjugation and release of doxorubicin for therapeutic applications.. Journal of Magnetism and Magnetic Materials 2011;323(2):237–43.
    doi: 10.1016/j.jmmm.2010.09.009google scholar: lookup
  19. Chang B, Zhang X, Guo J, Sun Y, Tang H, Ren Q, Yang W. General one-pot strategy to prepare multifunctional nanocomposites with hydrophilic colloidal nanoparticles core/mesoporous silica shell structure.. J Colloid Interface Sci 2012 Jul 1;377(1):64-75.
    doi: 10.1016/j.jcis.2012.03.082pubmed: 22520713google scholar: lookup
  20. Brockbank KG, MacLellan WR, Xie J, Hamm-Alvarez SF, Chen ZZ, Schenke-Layland K. Quantitative second harmonic generation imaging of cartilage damage.. Cell Tissue Bank 2008 Dec;9(4):299-307.
    doi: 10.1007/s10561-008-9070-7pubmed: 18431689google scholar: lookup
  21. He B, Wu JP, Kirk TB, Carrino JA, Xiang C, Xu J. High-resolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential.. Arthritis Res Ther 2014 Mar 12;16(2):205.
    doi: 10.1186/ar4506pmc: PMC4061724pubmed: 24946278google scholar: lookup
  22. Hall SA, Stucke D, Morrone B, Lebelt D, Zanella AJ. Simultaneous detection and quantification of six equine cytokines in plasma using a fluorescent microsphere immunoassay (FMIA).. MethodsX 2015;2:241-8.
    doi: 10.1016/j.mex.2015.04.002pmc: PMC4487921pubmed: 26150994google scholar: lookup
  23. Freedman JD, Lusic H, Wiewiorski M, Farley M, Snyder BD, Grinstaff MW. A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage.. Chem Commun (Camb) 2015 Jun 30;51(56):11166-11169.
    doi: 10.1039/c5cc03354cpmc: PMC4841792pubmed: 26051807google scholar: lookup
  24. Lakin BA, Ellis DJ, Shelofsky JS, Freedman JD, Grinstaff MW, Snyder BD. Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal.. Osteoarthritis Cartilage 2015 Dec;23(12):2158-2166.
    doi: 10.1016/j.joca.2015.05.033pmc: PMC4841831pubmed: 26067518google scholar: lookup
  25. Laurent D, Wasvary J, Rudin M, O'Byrne E, Pellas T. In vivo assessment of macromolecular content in articular cartilage of the goat knee.. Magn Reson Med 2003 Jun;49(6):1037-46.
    doi: 10.1002/mrm.10466pubmed: 12768582google scholar: lookup
  26. Burstein D, Velyvis J, Scott KT, Stock KW, Kim YJ, Jaramillo D, Boutin RD, Gray ML. Protocol issues for delayed Gd(DTPA)(2-)-enhanced MRI (dGEMRIC) for clinical evaluation of articular cartilage.. Magn Reson Med 2001 Jan;45(1):36-41.
    pubmed: 11146483doi: 10.1002/1522-2594(200101)45:1<36::aid-mrm1006>3.0.co;2-wgoogle scholar: lookup
  27. Kulmala KA, Korhonen RK, Julkunen P, Jurvelin JS, Quinn TM, Kröger H, Töyräs J. Diffusion coefficients of articular cartilage for different CT and MRI contrast agents.. Med Eng Phys 2010 Oct;32(8):878-82.
    doi: 10.1016/j.medengphy.2010.06.002pubmed: 20594900google scholar: lookup
  28. Lakin BA, Patel H, Holland C, Freedman JD, Shelofsky JS, Snyder BD, Stok KS, Grinstaff MW. Contrast-enhanced CT using a cationic contrast agent enables non-destructive assessment of the biochemical and biomechanical properties of mouse tibial plateau cartilage.. J Orthop Res 2016 Jul;34(7):1130-8.
    doi: 10.1002/jor.23141pmc: PMC5556386pubmed: 26697956google scholar: lookup
  29. Entezari V, Bansal PN, Stewart RC, Lakin BA, Grinstaff MW, Snyder BD. Effect of mechanical convection on the partitioning of an anionic iodinated contrast agent in intact patellar cartilage.. J Orthop Res 2014 Oct;32(10):1333-40.
    doi: 10.1002/jor.22662pubmed: 24961833google scholar: lookup
  30. Rothenfluh DA, Bermudez H, O'Neil CP, Hubbell JA. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage.. Nat Mater 2008 Mar;7(3):248-54.
    doi: 10.1038/nmat2116pubmed: 18246072google scholar: lookup
  31. McCaskill B. Effects of physiological dynamic compression loading on gold nanoparticle permeation of articular cartilage. Clemson University; 2012.
  32. Elsaid KA, Ferreira L, Truong T, Liang A, Machan J, D'Souza GG. Pharmaceutical nanocarrier association with chondrocytes and cartilage explants: influence of surface modification and extracellular matrix depletion.. Osteoarthritis Cartilage 2013 Feb;21(2):377-84.
    doi: 10.1016/j.joca.2012.11.011pmc: PMC3556184pubmed: 23186944google scholar: lookup
  33. Labens R, Lascelles BD, Charlton AN, Ferrero NR, Van Wettere AJ, Xia XR, Blikslager AT. Ex vivo effect of gold nanoparticles on porcine synovial membrane.. Tissue Barriers 2013 Apr 1;1(2):e24314.
    doi: 10.4161/tisb.24314pmc: PMC3879126pubmed: 24665389google scholar: lookup
  34. Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, Schlenk F, Fischer D, Kiouptsi K, Reinhardt C, Landfester K, Schild H, Maskos M, Knauer SK, Stauber RH. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology.. Nat Nanotechnol 2013 Oct;8(10):772-81.
    doi: 10.1038/nnano.2013.181pubmed: 24056901google scholar: lookup
  35. Lin Y-C. Novel organ culture model for a complete synovial joint: creation and application. 2015.
  36. Novakofski KD, Berg LC, Bronzini I, Bonnevie ED, Poland SG, Bonassar LJ, Fortier LA. Joint-dependent response to impact and implications for post-traumatic osteoarthritis.. Osteoarthritis Cartilage 2015 Jul;23(7):1130-7.
    doi: 10.1016/j.joca.2015.02.023pmc: PMC4778978pubmed: 25725390google scholar: lookup
  37. Elsaesser A, Howard CV. Toxicology of nanoparticles.. Adv Drug Deliv Rev 2012 Feb;64(2):129-37.
    doi: 10.1016/j.addr.2011.09.001pubmed: 21925220google scholar: lookup
  38. Hornos Carneiro MF, Barbosa F Jr. Gold nanoparticles: A critical review of therapeutic applications and toxicological aspects.. J Toxicol Environ Health B Crit Rev 2016;19(3-4):129-48.
    doi: 10.1080/10937404.2016.1168762pubmed: 27282429google scholar: lookup
  39. Huang H, Quan YY, Wang XP, Chen TS. Gold Nanoparticles of Diameter 13 nm Induce Apoptosis in Rabbit Articular Chondrocytes.. Nanoscale Res Lett 2016 Dec;11(1):249.
    doi: 10.1186/s11671-016-1461-2pmc: PMC4870655pubmed: 27178054google scholar: lookup
  40. Danscher G. Autometallography. A new technique for light and electron microscopic visualization of metals in biological tissues (gold, silver, metal sulphides and metal selenides).. Histochemistry 1984;81(4):331-5.
    pubmed: 6511487doi: 10.1007/bf00514327google scholar: lookup
  41. Kim EY, Moudgil KD. Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines.. Cytokine 2017 Oct;98:87-96.
    doi: 10.1016/j.cyto.2017.04.012pmc: PMC5581685pubmed: 28438552google scholar: lookup
  42. Lieberthal J, Sambamurthy N, Scanzello CR. Inflammation in joint injury and post-traumatic osteoarthritis.. Osteoarthritis Cartilage 2015 Nov;23(11):1825-34.
    doi: 10.1016/j.joca.2015.08.015pmc: PMC4630675pubmed: 26521728google scholar: lookup
  43. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.. Nat Rev Rheumatol 2011 Jan;7(1):33-42.
    doi: 10.1038/nrrheum.2010.196pubmed: 21119608google scholar: lookup
  44. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications.. Arthritis Res Ther 2017 Feb 2;19(1):18.
    doi: 10.1186/s13075-017-1229-9pmc: PMC5289060pubmed: 28148295google scholar: lookup
  45. Bertone AL, Palmer JL, Jones J. Synovial fluid cytokines and eicosanoids as markers of joint disease in horses.. Vet Surg 2001 Nov-Dec;30(6):528-38.
    pubmed: 11704948doi: 10.1053/jvet.2001.28430google scholar: lookup
  46. Page CE, Smale S, Carty SM, Amos N, Lauder SN, Goodfellow RM, Richards PJ, Jones SA, Topley N, Williams AS. Interferon-gamma inhibits interleukin-1beta-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis.. Arthritis Res Ther 2010;12(2):R49.
    doi: 10.1186/ar2960pmc: PMC2888198pubmed: 20307272google scholar: lookup
  47. Greenhill CJ, Jones GW, Nowell MA, Newton Z, Harvey AK, Moideen AN, Collins FL, Bloom AC, Coll RC, Robertson AA, Cooper MA, Rosas M, Taylor PR, O'Neill LA, Humphreys IR, Williams AS, Jones SA. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction.. Arthritis Res Ther 2014 Aug 30;16(4):419.
    doi: 10.1186/s13075-014-0419-ypmc: PMC4292830pubmed: 25175678google scholar: lookup
  48. Bogart LK, Pourroy G, Murphy CJ, Puntes V, Pellegrino T, Rosenblum D, Peer D, Lévy R. Nanoparticles for imaging, sensing, and therapeutic intervention.. ACS Nano 2014 Apr 22;8(4):3107-22.
    doi: 10.1021/nn500962qpmc: PMC4123720pubmed: 24641589google scholar: lookup
  49. Voss JR, Lu Y, Edwards RB, Bogdanske JJ, Markel MD. Effects of thermal energy on chondrocyte viability.. Am J Vet Res 2006 Oct;67(10):1708-12.
    doi: 10.2460/ajvr.67.10.1708pubmed: 17014320google scholar: lookup

Citations

This article has been cited 5 times.
  1. Farkaš B, de Leeuw NH. A Perspective on Modelling Metallic Magnetic Nanoparticles in Biomedicine: From Monometals to Nanoalloys and Ligand-Protected Particles. Materials (Basel) 2021 Jun 28;14(13).
    doi: 10.3390/ma14133611pubmed: 34203371google scholar: lookup
  2. Alvieri F, Mamani JB, Nucci MP, Oliveira FA, Filgueiras IS, Rego GNA, de Barboza MF, da Silva HR, Gamarra LF. Methods of Granulocyte Isolation from Human Blood and Labeling with Multimodal Superparamagnetic Iron Oxide Nanoparticles. Molecules 2020 Feb 11;25(4).
    doi: 10.3390/molecules25040765pubmed: 32053865google scholar: lookup
  3. Shreffler JW, Pullan JE, Dailey KM, Mallik S, Brooks AE. Overcoming Hurdles in Nanoparticle Clinical Translation: The Influence of Experimental Design and Surface Modification. Int J Mol Sci 2019 Nov 30;20(23).
    doi: 10.3390/ijms20236056pubmed: 31801303google scholar: lookup
  4. Vasiyani H. Chronic and non-canonical cGAS-STING activation: implications for health, disease, cancer, and emerging therapeutic opportunities. Apoptosis 2026 Feb 9;31(2):68.
    doi: 10.1007/s10495-026-02283-5pubmed: 41663856google scholar: lookup
  5. Küpper-Tetzel CP, Idris R, Kessel J, Schüttfort G, Hoehl S, Kohmer N, Graf C, Hogardt M, Besier S, Wichelhaus TA, Vehreschild MJGT, Stephan C, Wetzstein N. Coinfections and antimicrobial treatment in a cohort of falciparum malaria in a non-endemic country: a 10-year experience. Infection 2024 Apr;52(2):461-469.
    doi: 10.1007/s15010-023-02103-xpubmed: 37889376google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.