350 rub
Journal №10 for 2010 г.
Article in number:
DNA- nanotech drug delivery system based on hybrid metal-organic liquid crystalline nanocomposite is a tool for 157Gd -neutron-capture therapy against cancer
Authors:
O.V. Kondrashina, V.A. Bykov, A.I. Slivkin
Abstract:
Nanomedicine is a medical application of nanotechnology. Nanomedical approaches to drug delivery system develop nanoscale particles or molecules to improve the bioavailability of a drug. Poor bioavailability is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Neutron capture therapy (NCT) is a cancer treatment that utilizes nuclear neutron capture reaction (NCR) of radiation-producing elements administrated in vivo by thermal neutron irradiation. The success of gadolinium neutron-capture therapy (Gd-NCT) depends on a high accumulation of Gd atoms in the tumor. The first problem is the toxicity of free gadolinium even at low doses at its administration to tissues. The second problem is that a sufficient concentration of gadolinium could be retained in the tumor tissue during neutron irradiation after intratumoral injection despite capillary blood circulation within the tumor. Thus, the key factor in the success of the current Gd-NCT trial is the use of nanocoposite substances by means of Gd can be delivered efficiently and retained inside tumor tissues and/or cells during thermal neutron irradiation. In the present paper the efficiency of approach of nanotechnological liquid crystalline hybrid metal-organic drug delivery system was estimated. The goal of this nanodrug is cell destruction with Gd-NCT therapy. The main task of this work was evaluation of toxic activity of this substance for living cell and appraisal probability of using NCT. New nanotechnological liquid crystalline hybrid metal-organic drug delivery system based on DNA-Gd has excellent neutron capture properties because 157Gd has the highest thermal neutron capture cross section (255,000 barns) among naturally occurring isotopes. The local concentration of the rare earth elements in a particle is the highest nowadays. These nanoparticles are chemically inert so cell incubation with particles attached to their membranes do not lead to toxic effect. High affinity of those nanoparticles to cell membrane allows us to impact on cell more pointwisely and drastic then individual gadolinium atoms. This is the main advantage of this nanocomposite over other gadolinium carrier. Ionizing radiation of Gd atoms is affected not only directly by «burninig» membranes, cellular DNA and cytoplasm but also by free radical reactions. They last much longer then direct exposure to radiation and give cumulative effect. All these facts give every reason to assume that this nanomaterial is able to solve the main problems of Gd-NCT.
Pages: 17-23
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