Covalent functionalization of multi-walled carbon nanotubes with a gadolinium chelate for efficient T1-weighted magnetic resonance imaging

Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non-invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non-ionizing whole-body high field magnetic resonance imaging (MRI) is used to follow the distribution of water-dispersible non-toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd-CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd-CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd-CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd-CNTs is observed, confirming the evidences of other studies using different imaging modalities

The one year fate of iron oxide coated gold nanoparticles in mice

Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate

Magnetic Silica-Coated Iron Oxide Nanochains as Photothermal Agents, Disrupting the Extracellular Matrix, and Eradicating Cancer Cells

Cancerous cells and the tumor microenvironment are among key elements involved in cancer development, progression, and resistance to treatment. In order to tackle the cells and the extracellular matrix, we herein propose the use of a class of silica-coated iron oxide nanochains, which have superior magnetic responsiveness and can act as efficient photothermal agents. When internalized by different cancer cell lines and normal (non-cancerous) cells, the nanochains are not toxic, as assessed on 2D and 3D cell culture models. Yet, upon irradiation with near infrared light, the nanochains become efficient cytotoxic photothermal agents. Besides, not only do they generate hyperthermia, which effectively eradicates tumor cells in vitro, but they also locally melt the collagen matrix, as we evidence in real-time, using engineered cell sheets with self-secreted extracellular matrix. By simultaneously acting as physical (magnetic and photothermal) effectors and chemical delivery systems, the nanochain-based platforms offer original multimodal possibilities for prospective cancer treatment, affecting both the cells and the extracellular matrix

Etude du comportement in vivo de nanotubes de carbone simple paroi normaux et ultracourts

Les nanotubes de carbone simple paroi ultracourts (NTUC) présentent un intérêt particulier pour certaines applications biomédicales. Cependant, les données toxicologiques concernant ces nanostructures restent contradictoires. Ici, nous avons comparé le comportement in vivo de nanotubes de carbone simple paroi (NCPS) en fonction de la dose, de la longueur et des défauts de surface, après administration chez la souris. Dans un essai de toxicité aiguë, les NCPS ont été administrés per os à une dose allant de 50 à 1000 mg/kg de poids corporel. Aucun trouble de croissance ou effet létal n ont été observés. Néanmoins, après administration par voie ip, les NCPS, indépendamment de leur longueur ou de la dose administrée, peuvent s agréger in situ et former des structures fibreuses. Lorsque ces structures dépassent 10 m, elles provoquent la formation de granulomes. Les petits agrégats ne provoquent pas ce phénomène, mais ils persistent à l'intérieur des cellules 5 mois après administration. Cependant, les NCPS courts (< 300 nm) et bien individualisés échappent au système réticuloendothélial et sont excrétés par les reins et la voie biliaire. Ces derniers résultats suggèrent qu'il est possible d'utiliser les NCPS dans le domaine biomédical. Par ailleurs, il a été rapporté, qu'il existe un lien étroit entre le contenu carboné des macrophages alvéolaires (MA) et le déclin de la fonction pulmonaire. Or, le contenu carboné de ces MA, n'a été caractérisé que par microscopie optique. Dans la seconde partie de cette thèse, nous avons recherché et caractérisé à l'aide de techniques analytiques appropriées, la présence de particules carbonées (PC) dans les MA d'enfants parisiens. Nous montrons ici que la majeure partie des PC présentes dans les MA appartient à la famille des fullerènes y compris les NTCs. Cependant, dans les MA, les PC sont très rares et impossible à distinguer par microscopie optique des corps lamellaires, normalement présents dans les pneumocytes de type II.Carbon nanotube (CNT) materials are of special interest as potential tools for biomedical applications. However, available toxicological data concerning single-walled carbon nanotubes (SWNTs) remain contradictory. Here, we compared the effects of SWNTs as a function of dose, length and surface chemistry in Swiss mice. In an acute toxicity test, SWNTs were administered orally at a dose level up to 1000 mg/kg bodyweight (b.w.). Neither death nor growth or behavioral troubles were observed. After intraperitoneal administration, SWNTs, irrespective of their length or dose (50-1000 mg/kg b.w.), can coalesce inside the body to form fiber-like structures. When structure lengths exceeded 10 m, they irremediably induced granuloma formation. Smaller aggregates did not induce granuloma formation, but they persisted inside cells for up to 5 months after administration. Short (<300 nm) well-individualized SWNTs can escape the reticuloendothelial system and are excreted through the kidneys and bile ducts. These findings suggest that if the potential of SWNTs for medical applications is to be realized, they should be engineered into discrete, individual particles. Moreover, it has been shown recently, that there is a link between airborne fine particulate matter and decline in lung function. We report here that a large portion of the carbonaceous particles engulfed by the airway macrophages of Parisian asthmatic infants and children are aggregated fullerene-like structures, including CNTs. Furthermore, the presence of SWNTs in the macrophages has been confirmed by their characteristic near-infrared fluorescence emission spectrum. These findings suggest that humans are being routinely exposed to anthropogenic CNTs.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Cell labeling with magnetic nanoparticles: Opportunity for magnetic cell imaging and cell manipulation

International audienceThis tutorial describes a method of controlled cell labeling with citrate-coated ultra small superparamagnetic iron oxide nanoparticles. This method may provide basically all kinds of cells with sufficient magnetization to allow cell detection by high-resolution magnetic resonance imaging (MRI) and to enable potential magnetic manipulation. In order to efficiently exploit labeled cells, quantify the magnetic load and deliver or follow-up magnetic cells, we herein describe the main requirements that should be applied during the labeling procedure. Moreover we present some recommendations for cell detection and quantification by MRI and detail magnetic guiding on some real-case studies in vitro and in vivo

Electric field-responsive nanoparticles and electric fields: physical, chemical, biological mechanisms and therapeutic prospects

International audienceElectric fields are among physical stimuli that have revolutionized therapy. Occurring endogenously or exogenously, the electric field can be used as a trigger for controlled drug release from electroresponsive drug delivery systems, can stimulate wound healing and cell proliferation, may enhance endocytosis or guide stem cell differentiation. Electric field pulses may be applied to induce cell fusion, can increase the penetration of therapeutic agents into cells, or can be applied as a standalone therapy to ablate tumors. This review describes the main therapeutic trends and overviews the main physical, chemical and biological mechanisms underlying the actions of electric fields. Overall, the electric field can be used in therapeutic approaches in several ways. The electric field can act on drug carriers, cells and tissues. Understanding the multiple effects of this powerful tool will help harnessing its full therapeutic potential in an efficient and safe way

Cycle de vie de nanoparticules magnétiques dans l’organisme

Malgréune utilisation toujours croissante de nanomatériaux, leur devenir dans l’organisme reste peu étudié et mal connu. Une meilleure compréhension des interactions entre nanoparticules et environnement biologique est nécessaire pour maîtriser une éventuelle toxicité et développer leurs applications médicales. Dans cet objectif, il est urgent de développer des méthodologies pour détecter, quantifier et suivre l’évolution de nanoparticules dans un milieu biologique complexe en couvrant les échelles pertinentes, du nanomètre au tissu. Dans ce travail, nous décrirons le cycle de vie de nanoparticules magnétiques dans l’organisme, en suivant leurs transformations au cours du temps, de l’injection à l’élimination. Contrairement aux approches de nanotoxicologie, nous adoptons le point de vue des nanoparticules pour identifier l’influence de l’environnement biologique sur leurs propriétés et leur devenir (interactions avec les protéines, confinement cellulaire, dégradation...). Il s’agit d’établir des liens entre la structure initiale des nanoparticules et leur cycle de vie