Spelling suggestions: "subject:"theranostic agents"" "subject:"theranostics agents""
1 |
Ultra-short, Single-walled Carbon Nanotube Capsules for Diagnostic Imaging and RadiotherapyMatson, Michael 24 July 2013 (has links)
This thesis is centered on the Gadonanotubes (GNTs), an ultra-high-performance magnetic resonance imaging (MRI) contrast agent material discovered in our laboratories in 2005. The GNTs are a new paradigm in MRI contrast agent design with small clusters of Gd3+ ions within ultra-short carbon nanocapsules (ca. 50 nm) cut from full-length single-walled carbon nanotubes. Here, the factors underlying the performance efficacy of the GNTs have been investigated for the first time by variable-field (-50,000 Oe to 50,000 Oe at 2K) and variable-temperature (2K to RT at 100 Oe) magnetic susceptibility measurements using a Magnetic Property Measurement System (MPMS, based on a SQUID magnetometer). Additionally, experiments focused on the effects of hydroxylation of the GNTs’ exterior surface regarding water-solubility are examined. Finally, the use of the GNTs as potential replacements for traditional metal-chelating/sequestering agents is explored. More specifically, the internal Gd3+-ion clusters of the GNTs have been radiolabeled: (1) with 153Gd3+ ions to test Gd3+-ion stability to simulated biological challenge, (2) with 225Ac3+ ions to generate a new concept for a GNT-based agent for α-radiotherapy, and finally (3) with 64Cu2+ ions to produce the first bimodal MRI/PET (PET = positron emission tomography) imaging agent derived from the GNTs.
|
2 |
Novel Lanthanide Containing Polymers for Nucleic Acid Delivery and Monitoring of Polyplex DynamicsKelkar, Sneha S. 14 March 2013 (has links)
Nucleic acid therapy holds real promise to offer less severe (lower side effects) as a treatment for life threatening and difficult to treat diseases such as cancer, heart disease or Alzheimer's disease. Theranostic nanomaterials that combine diagnostic imaging and therapeutic delivery, have potential to minimize the amount of time and dosage required for the treatment. This is achieved via delivery of nanoparticles that carry therapeutic payload as well as imaging agents; these agents need to circulate in the body longer due to its (larger) size and selectively accumulate in the tumor regions through the enhanced permeability and retention (EPR) effect.
We have designed novel lanthanide (Gd, Tb or La) containing polymers with oligoethyleneamine and lanthanide chelating units to incorporate DNA binding and imaging agent functionality. Protonable amines along the polymer backbone electrostatically interact with DNA and compact it into a nanoparticle. These nanoparticles can be imaged both in vivo (Gd analogues, magnetic resonance imaging) and intracellularly (Tb chelation, fluorescence spectroscopy). Polymers were synthesized via step-growth polymerization to achieve a degree of polymerization of 18-24 for different analogues with varying amine number (three to six, N3-N6) along the backbone. Dynamic light scattering performed on the polyplexes (polymer-DNA complexes) indicate that they are in nanometer size range (50-80nm). All the polymers used to form polyplexes exhibited low toxicity to cultured human Glioblastoma cells (U-87) and showed variable transfection efficiency dependent on structure, comparable to G4 (sold as Glycofect"), a commercial transfection agent previously developed in our lab.
This dissertation describes the first studies by the Reineke lab to monitor polyplex formation and destabilization using lanthanide resonance energy transfer (LRET). Polyplexes were formulated with Tb chelated N5 polymer and tetramethyl rhodamine (TMR) labeled pDNA, which are "LRET pairs". We observed decrease in luminescence intensity of Tb polymer (donor) in close proximity of TMR DNA (acceptor) in an intact polyplex at different N/P ratios. However, upon destabilization of polyplexes by addition of salt or heparin solution, the increase in distance between donor and acceptor resulted in increase in the luminescence intensity of Tb polymer. With the LRET technique, we are able to monitor formation and destabilization of polyplexes by monitoring change in luminescence of the donor chromophore (Tb).
Polyplexes formulated with non-paramagnetic analogues (La chelated) of N4, polyethyleneimine (PEI) and G4 were studied using NMR to quantify free vs. bound polymer in a formulation. The amount of free polymer was measured by integrating the broad resonances from nanometer-sized particles (polyplexes) with narrow peaks from free polymer chains. This was supported by using an internal reference method to quantify free polymer amount from known internal reference concentration. We observed an increase in the amount of free polymer with N/P ratio for all three systems and both the methods showed comparable results. / Ph. D.
|
3 |
Synthesis and Application of Polymer Stabilized, Water Dispersible Copper Based Nanoparticles as Anti-cancer and Diagnostic AgentsYARABARLA, SRIRAMAKRISHNA 24 April 2017 (has links)
No description available.
|
4 |
Synthèse de complexes organobimétalliques à activité biologique / Synthesis of organobimetallic complexes with biological activityWenzel, Margot 22 October 2013 (has links)
Un axe de recherche particulièrement développé en chimie organométallique moderneconcerne la recherche d’agents chimiothérapeutiques alternatifs au cisplatine dans lestraitements contre le cancer. Dans ce domaine, plusieurs stratégies ont été développées depuisplusieurs dizaines d’années, parmi lesquelles nous pouvons citer la multinucléarité, consistanten la création d’édifices polymétalliques. L’objectif de la première partie de ce manuscrits’inscrit dans cette thématique, par la conception, l’obtention et l’étude des propriétésbiologiques de complexes hétérobimétalliques "early-late" (Ti-Ru, Ti-Au, Ti-Pt, Ti-Os, Ti-Rh, Ti-Ir) et "late-late" (Pt-Au). Un deuxième concept développé au cours de ce manuscritconsiste en la génération de nouvelles espèces théranostiques, par association au sein d’unmême complexe d’un fragment métallique à activité thérapeutique et d’une sonde fluorescentepermettant de visualiser le trajet et les cibles biologiques de ce premier. Dans ce cadre, deuxséries parallèles de complexes bimétalliques ont été synthétisées à partir des squelettesRu(bipy)32+ et Ru(bipy)2(dipy)2+ dont les propriétés de luminescence ont été largementdécrites et utilisées pour diverses applications. Ces composés bimétalliques ont pu fairel’objet de mesures sur les deux fronts, à savoir leur activité cytotoxique envers des lignéescellulaires cancéreuses et leurs propriétés photophysiques. / A research theme especially developed in modern organometallic chemistry deals withnew chemotherapeutic agents as alternatives to cisplatin for the treatments against cancer. Inthis area, several strategies have been considered since decades, among which one can citemultinuclearity, meaning the creation of polymetallic structures. The objective of the first partof this manuscript deals with this theme, with the design, synthesis and study of the biologicalproperties of "early-late" hetero-bimetallic complexes (Ti-Ru, Ti-Au, Ti-Pt, Ti-Os, Ti-Rh, Ti-Ir) and "late-late" (Pt-Au). A second concept developed in this thesis consists in thegeneration of new theranostic agents by association inside a same unit of a metal fragmentwith therapeutic activity, and of a fluorescent probe allowing the visualization of thebiological targets. In this field, two parallel series of bimetallic compounds have beenobtained based on the skeletons Ru(bipy)32+ and Ru(bipy)2(dipy)2+, whose luminescenceproperties have been widely described and used for several applications. These bimetalliccomplexes have been tested both for their cytotoxic activity against cancer cells lines andtheir photophysical properties.
|
Page generated in 0.0694 seconds