RESUMO
An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2â³-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3 T, 7 T and 9.4 T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. In vitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2 mM [Gd] concentration. In vivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2 mM [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0 mM [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0 mM [Gd]). The DO3A-Lys has been labeled with (68)Ga radioisotope for biodistribution studies. (68)Ga(DO3A-Lys) has high uptake in both HT1080 and U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and displays promising characteristics of an MRI contrast agent for tumor angiography.
Assuntos
Angiografia/métodos , Meios de Contraste , Compostos Heterocíclicos/administração & dosagem , Lisina/química , Imageamento por Ressonância Magnética/métodos , Neoplasias/irrigação sanguínea , Compostos Organometálicos/administração & dosagem , Animais , Feminino , Gadolínio/administração & dosagem , Gadolínio/química , Gadolínio/farmacocinética , Meia-Vida , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacocinética , Humanos , Camundongos , Camundongos SCID , Compostos Organometálicos/química , Compostos Organometálicos/farmacocinética , Distribuição TecidualRESUMO
A series of organic cations, such as triphenylphosphonium (TPP), 2-(diphenylphosphoryl)-ethyldiphenylphosphonium (TPEP), represent molecular probes for imaging tumors. These organic cations have been labeled with 64Cu radioisotope for imaging tumors by positron emission tomograghy (PET). Among these organic cation ligands, TPEP was selected for extensive evaluation using magnetic resonance imaging (MRI) based on its higher tumor uptake and better Tumor/Background (T/B) ratios. This report presents the development of a new Gd(III) chelate [Gd(DO3A-xy-TPEP)]⺠as a cationic MRI contrast agent. The contrast agent was synthesized and characterized in vitro and in vivo. In vitro cell viability showed low cytotoxicity at low [Gd] concentrations. Cell uptake experiment shows that the [Gd(DO3A-xy-TPEP)]⺠has high affinity for tumor cells. The in vitro T1 relaxivity measured at 9.4 T is about 50% higher than those of contrast agents in clinical use: Gd-DTPA (Magnevist) and Gd-DOTA (Dotarem). In vivo imaging studies in tumor-bearing mice at 7.0 T demonstrated significant signal enhancement at the site of the tumors. [Gd(DO3A-xy-TPEP)]⺠is a promising tumor-targeting MRI contrast agent for diagnostic imaging.
Assuntos
Meios de Contraste/química , Gadolínio/química , Imageamento por Ressonância Magnética/métodos , Meglumina/química , Compostos Organometálicos/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Células HeLa , Compostos Heterocíclicos/química , Humanos , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Nanoporous alumina (PA) arrays produced by self-ordering growth, using electrochemical anodization, have been extensively explored for potential applications based upon the unique thermal, mechanical and structural properties, and high surface-to-volume ratio of these materials. However, the potential applications and functionality of these materials may be further extended by molecular-level engineering of the surface of the pore rims. In this paper we present a method for the generation of chemical gradients on the surface of PA arrays based upon plasma co-polymerization of two monomers. We further extend these chemical gradients, which are also gradients of surface charge, to those of bound ligands and number density gradients of nanoparticles. The latter represent a highly exotic new class of materials, comprising aligned PA, capped by gold nanoparticles around the rim of the pores. Gradients of chemistry, ligands and nanoparticles generated by our method retain the porous structure of the substrate, which is important in applications that take advantage of the inherent properties of these materials. This method can be readily extended to other porous materials.
RESUMO
Nanotubular titanium oxide (TiO(2)) produced by self-ordering processes using electrochemical anodization have been extensively explored in recent years as a new biomaterial for implants, drug delivery systems, cell growth, biosensors, immunoisolations, bioartificial organs and tissue engineering. Chemical inertness is the main weakness of this material when placed in contact with biological systems and surface modification is a possible solution of this problem. The aim of this study is to develop a flexible and facile method for surface modification of TiO(2) nanotubes to tailor new interfacial properties important in many biomedical applications. TiO(2) nanotubes were prepared by electrochemical anodization of titanium foil using ethylene glycol: NH(4)F electrolyte (2% water and 0.3% NH(4)F). Plasma surface modification using allylamine (AA) as a precursor has been applied to generate a thin and chemically reactive polymer (AAPP) film rich in amine groups on top of the TiO(2) nanotube surface. This initial polymer film was used for further surface functionalization by attachment of desired molecules. Two modification techniques were used to demonstrate the flexibility for building of new functionalities on titania nanotube surface: electrostatic adsorption of poly(sodium styrenesulfonate) (PSS) as an example of layer-by-layer assembly (LbL), and covalent coupling of poly(ethylene glycol) (PEG) as an example of creating a protein-resistant surface. These approaches for tailoring the surface chemistry and wettability of TiO(2) nanotubes offer considerable prospects for advancing their interfacial properties to improve existing and develop new functional biomaterials for diverse biomedical applications.