The use of functionalization applied to nanobiotechnology:Targeting cancer stem cells and regioselective functionalization of phages
| Autor: | Piñol Domingo, Carlos, Goya, Gerardo Fabián, Visus Miguel, María Carmen, Grelet, Eric |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname |
| Popis: | This work, composed of two subprojects, has been developed within the framework of two independent research lines on the functionalization and application of nanoprobes to nanobiotechnology field, specifically in biomedicine or biotechnology. The multidisciplinary research proposal involves physicists, chemists, biochemists and medical doctors, and therefore a part of the student’s training work was performed at several centers abroad: The Hillman Cancer Center (UPCI), Pittsburgh, USA; the Centre de Recherche Paul Pascal (CRPP), Bordeaux and the Institut National de la Recherche Agronomique (BFP-IBVM), Villenave d’Ornon, France. Example 1. The Cancer Stem Cell (CSCs) concept says that only a small proportion of cells within the tumor have tumorigenic capacity. These cells are usually chemo and radio resistance that is why it is believed that are responsible for tumor relapse and recurrence of cancer patients. There is an urgent need to develop cancer therapies that are effective in killing these specific tumor cells. Magnetic nanoparticles (MNPs), functionalized with specific monoclonal antibodies, can be generated to recognize CSCs target molecules within the tumors. Hyperthermia is a new approach of using these MNPs positioned in an alternating magnetic field (AMF) to produce localized heat and kill CSCs. Magnetic nanoparticles-induced hyperthermia is under investigation in different clinical trials on cancer patients. However, there is no information available on whether hyperthermia can eliminate CSCs. Therefore, the final goal of this project involve the application of hyperthermia to destroy CSCs and study the effect of this treatment in reducing tumor growth, increased cell death and improving the response to conventional therapies as chemo-radio therapy. More particularly, this work has focused on the first steps of this strategy related to the preparation of antibody-functionalized MNPs (MNPs:anti-CDs) and their application to target CSCs for several tumor cell lines by fluorescence microscopy. It has also been supplemented with cytotoxicity studies by MTT assays and surface and intracellular distribution studies by scanning electron microscopy (SEM) technique. Example 2. It is known that elongated viruses in concentrated solution self-organize into liquid-crystalline structures (mesophases) which exhibit different intermediate states between disordered liquids and perfectly organized crystals. Therefore, the introduction of specific functions by molecule grafting or nanoparticle bonding on the viral particles with a precise positional control, combined with the self-assembly properties of these functionalized bioparticles, would give access to a wide range of applications in biosensing, memory devices, nanocircuits, light-harvesting systems, nanobatteries or MRI contrast agents. We used the mutant M13-C7C phage which presents a genetic mutation that allows the creation of unique binding sites on only one end of the filamentous virus through a pair of cysteine residues. The final goal of the project is to develop hybrid materials formed by the monitored assembly of these mutant M13-C7C phages with magnetic nanoparticles, with a 1:1 molar ratio, to induced highly sensitive nanorods by magnetic field, which are otherwise absent from the viral coat protein of the wild type phage. More specifically, this work has focused in the mass production, amplification and purification processes, of the mutant M13-C7C phage which is during its growth in competition with the wild type one. We have then specifically studied the functionalization of these mutant phages with maleimide fluorophores, followed by the self-organization properties in order to validate our scientific approach. • Keywords: Nanobiotechnology; Nanofunctionalization; Cancer stem cells (CSCs); Magnetic nanoparticles (MNPs); Monoclonal antibodies; Viral nanoparticles (VNPs); Liquid crystalline structures. |
| Databáze: | OpenAIRE |
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