In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

Abstract

Achraf Al Faraj1,2, Florence Fauvelle3, Nathalie Luciani4, Ghislaine Lacroix5, Michael Levy4, Yannick Crémillieux1, Emmanuelle Canet-Soulas1Université Lyon1, Créatis-LRMN, Lyon, France; 2King Saud University, College of Applied Medical Sciences, Radiological Sciences Department, Riyadh, Kingdom of Saudi Arabia; 3CRSSA, Biophysique Cellulaire et Moléculaire, Laboratoire de RMN, La Tronche, France; 4Université Paris7-Paris Diderot, Matières et Systèmes Complexes, Paris, France; 5Institut National de l’Environnement et des Risques Industriels, Verneuil-en-Halatte, FranceBackground: Single-walled carbon nanotubes (SWCNT) hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescently-labeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required.Methods: In this study, noninvasive in vivo magnetic resonance imaging (MRI) investigations combined with high-resolution magic angle spinning (HR-MAS), Raman spectroscopy, iron assays, and histological analysis ex vivo were proposed and applied to assess the biodistribution and biological impact of intravenously injected pristine (raw and purified) and functionalized SWCNT in a 2-week longitudinal study. Iron impurities allowed raw detection of SWCNT in vivo by susceptibility-weighted MRI.Results: A transitional accumulation in the spleen and liver was observed by MRI. Raman spectroscopy, iron assays, and histological findings confirmed the MRI readouts. Moreover, no acute toxicological effect on the liver metabolic profile was observed using the HR-MAS technique, as confirmed by quantitative real-time polymerase chain reaction analysis.Conclusion: This study illustrates the potential of noninvasive MRI protocols for longitudinal assessment of the biodistribution of SWCNT with associated intrinsic metal impurities. The same approach can be used for any other magnetically-labeled nanoparticles.Keywords: single-walled carbon nanotubes, magnetic resonance imaging, high resolution magic angle spinning