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Biological Effect Of Nano-inorganic Layered Double Hydroxides As A Drug Delivery System During It Interacted With Hela Cell Line

Posted on:2009-08-08Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiFull Text:PDF
GTID:2121360245957972Subject:Biochemistry and Molecular Biology
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During the past several years, many targeting nano-drug-delivery systems have been intensively explored for tumor diagnostics and therapeutics. Especially, there has been rapid expansion of the development of bioinorganic hybrid systems for drug delivery. Among a variety of inorganic materials, layered double hydroxides (LDHs) are endowed with great potential as an inorganic matrix for this purpose. LDH is not only the uniqueness nanomaterial which could biodegradation in biosystem, but also do not need modification for cellular delivery. For example, Folinic acid and Methotrexate hybridized with LDH facilitates delivery efficiency, and the intercalation of sulfobutyl ether b-cyclodextrin into Mg-Al-LDH was examined aiming for the controlled release of drugs.The continuous development of new drug delivery systems is driven by the need to maximize therapeutic activity while minimizing negative side effects. Previous research have been reported that some nanomaterials could exhibit unexpected toxicity to living organisms, and understanding of the potential health risks associated with nanomaterial use in biomedicine is extremely limited. Although some research mentioned LDH is a relative safe nano-drugcarrier, it is still have to face another problem, that is how to find out a balancing dosage which could lead no harmful to biosystem during maximize therapeutic activity.Measurement of oxidative stress was suggested to be one of the best ways to find out if nanomaterials are toxic, and even could find fundamental cause-effect relationship of nanotoxicology. There is a direct relationship between the surface area, reactive oxygen species (ROS)-generating capability, and proinflammatory effects of nanoparticles. From a mechanistic perspective, ROS generation and oxidative stress is the best developed paradigm to explain the toxic effects of inhaled nanoparticles. Under normal coupling conditions in the mitochondrion, ROS are generated at low frequency and are easily neutralized by antioxidant defenses such as glutathione (GSH) and antioxidant enzymes. However, under conditions of excess ROS production, such as may occur in the lung and possibly the circulatory system during ambient or occupational nanoparticle exposures, the natural antioxidant defenses may be overwhelmed. Oxidative stress refers to a state in which glutathione (GSH) is depleted while oxidized glutathione (GSSG) accumulates. Cells respond to this drop in the GSH/GSSG ratio by mounting protective or injurious responses.We also choose DNA strand break (DSB), DNA-Protein crosslink (DPC) and carbonyl content in proteins (CCP) as biomonitor. Because any group modificaton of DNA and Protein could be regard as a signal of cancer. In addition, endogenous nitric oxide (eNO) is a ubiquitous biologically active substance produced from the oxidative metabolism of L-arginine by nitric oxide synthases in the presence of oxygen and a variety of co-factors. Under favorable conditions NO may promote a variety of oxidative modifications of proteins and other biomolecules.All results demonstrated that nano-LDH should not induce obvious oxidative stress effects of Hela cell system, and it have the potential to used as drug vehicle in biomedicine field. However further study is still be needed in vivo system.
Keywords/Search Tags:Nano-Layered Double Hydroxide (nano-LDH), Oxidative stress, Reactive oxygen species (ROS), Glutathione (GSH), Endogenous nitric oxide (eNO), DNA strand break (DSB), DNA-Protein crosslink (DPC), Carbonyl content in proteins (CCP)
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