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Highly Biocompatible TiO2:Gd3+ Nano-contrast Agent with Enhanced Longitudinal Relaxivity for Targeted Cancer Imaging

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Nanoscale

Source : Nanoscale, Volume 3, Number 10, p.4150-4161 (2011)

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Keywords : Adsorbed water, Adverse effect, Air-annealing, Amorphous phase, Amorphous TiO, article, biocompatibility, Biocompatible Materials, biomaterial, Blood, Cancer cells, Cancer imaging, Cell culture, Cell Line, Cell lines, cell membrane, Cell membranes, cell viability, chemistry, Coagulation, Contrast Media, contrast medium, Crystalline hosts, Crystalline materials, cytokine, Cytokines, Diseases, Doped titania, Endothelial cells, Fibroblast cells, Folate receptor, Folic acids, gadolinium, Hemolysis, human, Human bloods, Human peripheral blood, Humans, Intravenous administration, Magnetic resonance, Magnetic Resonance Imaging, Medical imaging, metabolism, metal nanoparticle, Metal Nanoparticles, Molecular receptors, MR imaging, Nanomagnetics, neoplasm, Neoplasms, nuclear magnetic resonance imaging, Organic acids, pathology, Peripheral blood mononuclear cells, Plasma coagulation, Platelet aggregation, Proton-exchange, Re-arrangement, Reactive oxygen, reactive oxygen metabolite

Campus : Kochi

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences and Molecular Medicine, Nanosciences

Year : 2011

Abstract : We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd3+ doped amorphous TiO2 of size ∼25 nm, exhibiting enhanced longitudinal relaxivity (r1) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r 1 relaxivity which is ∼2.5 fold higher than the commercially used CA Magnevist™. The crystalline (anatase) samples formed by air annealing at 250 °C and 500 °C showed significant reduction in r1 values and MR contrast, which is attributed to the loss of proton-exchange contribution from the adsorbed water and atomic re-arrangement of Gd 3+ ions in the crystalline host lattice. Nanotoxicity studies including cell viability, plasma membrane integrity, reactive oxygen stress and expression of pro-inflammatory cytokines, performed on human primary endothelial cells (HUVEC), human blood derived peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma (KB) cell line showed excellent biocompatibility up to relatively higher doses of 200 μg ml-1. The potential of this nano-CA to cause hemolysis, platelet aggregation and plasma coagulation were studied using human peripheral blood samples and found no adverse effects, illustrating the possibility of the safe intravenous administration of these agents for human applications. Furthermore, the ability of these agents to specifically detect cancer cells by targeting molecular receptors on the cell membrane was demonstrated on folate receptor (FR) positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA showed receptor specific accumulation on cell membrane while leaving the normal fibroblast cells (L929) unstained. This study reveals that the Gd3+ doped amorphous TiO2 nanoparticles having enhanced magnetic resonance contrast and high biocompatibility is a promising candidate for molecular receptor targeted MR imaging. © 2011 The Royal Society of Chemistry.

Cite this Research Publication : P. Chandran, Abhilash Sasidharan, Anusha Ashokan, Dr. Deepthy Menon, Shantikumar V Nair, and Dr. Manzoor K., “Highly Biocompatible TiO2:Gd3+ Nano-contrast Agent with Enhanced Longitudinal Relaxivity for Targeted Cancer Imaging”, Nanoscale, vol. 3, pp. 4150-4161, 2011.

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