Cellular uptake and imaging studies of gadolinium-loaded single-walled carbon nanotubes

postprintThe 18th Joint Annual Meeting of ISMRM-ESMRMB, Stockholm, Sweden, 1-7 May 2010

Scaling behaviour for the water transport in nanoconfined geometries

The transport of water in nanoconfined geometries is different from bulk phase and has tremendous implications in nanotechnology and biotechnology. Here molecular dynamics is used to compute the self-diffusion coefficient D of water within nanopores, around nanoparticles, carbon nanotubes and proteins. For almost 60 different cases, D is found to scale linearly with the sole parameter theta as D(theta)=DB[1+(DC/DB-1)theta], with DB and DC the bulk and totally confined diffusion of water, respectively. The parameter theta is primarily influenced by geometry and represents the ratio between the confined and total water volumes. The D(theta) relationship is interpreted within the thermodynamics of supercooled water. As an example, such relationship is shown to accurately predict the relaxometric response of contrast agents for magnetic resonance imaging. The D(theta) relationship can help in interpreting the transport of water molecules under nanoconfined conditions and tailoring nanostructures with precise modulation of water mobility

Physicochemical Characterization, and Relaxometry Studies of Micro-Graphite Oxide, Graphene Nanoplatelets, and Nanoribbons

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents

New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging

Background: Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein. Methodology/Principal Findings: The first approach utilizes three-legged clathrin triskelia modified to carry 81 gadolinium chelates. The second approach uses clathrin cages self-assembled from triskelia and designed to carry 432 gadolinium chelates. Clathrin triskelia and cages were characterized by size, structure, protein concentration, and chelate and gadolinium contents. Relaxivity was evaluated at 0.47 T. A series of studies were conducted to ascertain whether fluorescent-tagged clathrin nanoplatforms could cross the blood brain barriers (BBB) unaided following intranasal, intravenous, and intraperitoneal routes of administration. Clathrin nanoparticles can be constituted as triskelia (18.5 nm in size), and as cages assembled from them (55 nm). The mean chelate: clathrin heavy chain molar ratio was 27.0464.8: 1 fo

Comparison of gadolinium loaded and empty carbon nanotubes as high performance MRI contrast agent

Abstract no. J080Molecular Imaging and Biology, 2009, v. 12, suppl. 1, p. S41-S42Introduction: Gadolinium loaded ultra-short single walled carbon nanotubes (US-tubes) has been proposed as an effective high r2 relaxivity contrast agent for use in MR molecular imaging. However, the true active ingredients for inheriting its high performance r2 characteristics, is remain unknown. In this study, we compare the R2 and R2* relaxation rate of the US-tubes with/without Gadolinium ions encapsulation. Methods: Two types of US-tubes MRI phantoms were prepared: (i) Gadonanotubes with 41 μM Gd and (ii) empty US-tubes. Each type of nanotubes was dispersed in pluronic solution with carbon concentration of 275 mg/L and transferred to a 1 cc syringe for MRI imaging. MRI imaging was performed in a 3T MRI scanner using a 35 mm volume coil with 2D spin echo (TR=1500 ms, TE=20–80 ms with 10 ms increment) and 2D gradient echo (alpha=90, TR=1500 ms, TE=20–80 ms with 5 ms increment) sequences to evaluate the R2 and R2* respectively. A 1 mm thick single slice was obtained at each TE cutting in the middle of the 3.5 cm long filled syringe placed parallel to the main magnetic field. T2 and T2* were determined by linear fitting of the measured image intensities at each TE at each phantom into log(S) = log(S0)-TE/T2 and log(S) = log(S0)-TE/T2*. Results and Discussions: Table 1 shows the estimated R2 and R2* relaxation rates of the phantoms. R2 represents the coefficient of determinations of the linear fitting. Both Gadonanotubes and empty US-tubes show high R2 and R2* relaxation rates with the R2* being 6–11% stronger than R2. The slight increase in R2* may attribute to bulk magnetic susceptibility effects due to the presence of metal ions inside the US-tubes. Nethertheless,the R2* observed is small when compared with that of other superparamagnetic contrast agents which usually show a few times increase in R2*. This may be due to the low concentration (in μM) and lose density packing of the metal ions inside the tubes. For empty US-tubes, it is observed that its relaxivities are as good as Gadolinium loaded US-tubes. Additional Gd3+ loading does not significantly increase the relaxivities of the US-tubes. Therefore, it is reasonable to consider using empty US-tubes as a high performance MRI contrast agent as well as drug/gene delivery carrier, with the delivery items being encapsulating inside its hollow interior space

Cellular uptake and imaging studies of gadolinium-loaded single-walled carbon nanotubes as MRI contrast agents

We quantify here, for the first time, the intracellular uptake (J774A.1 murine macrophage cells) of gadolinium-loaded ultra-short single-walled carbon nanotubes (gadonanotubes or GNTs) in a 3 T MRI scanner using R 2 and R 2* mapping in vitro. GNT-labeled cells exhibited high and linear changes in net transverse relaxations (ΔR 2 and ΔR2*) with increasing cell concentration. The measured ΔR 2* were about three to four times greater than the respective ΔR 2 for each cell concentration. The intracellular uptake of GNTs was validated with inductively coupled plasma optical emission spectrometry (ICP-OES), indicating an average cellular uptake of 0.44±0.09pg Gd per cell or 1.69×10 9 Gd 3+ ions per cell. Cell proliferation MTS assays demonstrated that the cells were effectively labeled, without cytotoxicity, for GNTs concentrations ≤28μM Gd. In vivo relaxometry of a subcutaneously-injected GNT-labeled cell pellet in a mouse was also demonstrated at 3 T. Finally, the pronounced R 2* effect of GNT-labeled cells enabled successful in vitro visualization of labeled cells at 9.4 T. © 2010 John Wiley & Sons, Ltd.link_to_subscribed_fulltex

Does a Narrow Definition of Medical Professionalism lead to Systemic Bias and Differential Outcomes?

The concept of medical professionalism is enshrined in the principles of Good Medical Practice (GMP), upheld by the General Medical Council (GMC), and is applicable to all doctors as well as undergraduate students in the United Kingdom. The principles were conceived, developed and implemented to ensure that the highest standards of medical practice are adhered to for the safety of the public and to retain trust in the medical profession. The GMC has a statutory duty to ensure that professional standards are maintained. Approximately 1% of doctors on the medical register are subject to investigation by the GMC, based on referrals made by employing organisations or the public.&#x0D; While appropriate GMC investigation is essential to maintain standards, patient safety and public confidence, there are inherent inequalities in the process resulting in widely different outcomes for certain groups of students or doctors based on Black and minority ethnicity, male gender and non-UK primary medical qualification often leading to devastating consequences.&#x0D; This narrative review considers the contributors to differential attainment (DA) and the impact on the health service, patients and individual wellbeing. It explores the tenets of a current narrow definition of professionalism which, while representing the unidimensional White majority view, ignores the huge diversity of the workforce and the public, thus exposing significant tensions for groups of professionals.  The Covid-19 pandemic has exposed the inherent systemic bias in the health service for both professionals and the public. This review recommends root and branch reform of the definition of professionalism, by engagement with the public and the workforce, to incorporate principles of equality, diversity and inclusion, which the authors believe will create the environment for a just and equitable professional experience. 1 </jats:p