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Identification Of Physicochemical Features Of GNPs For TNF-α Secretion In Macrophages

Posted on:2017-01-09Degree:MasterType:Thesis
Country:ChinaCandidate:Y L WangFull Text:PDF
GTID:2271330485482056Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
In recent years, due to their special properties that different from macroscopic matter (photoelectric effect, surface effect, small size effect, etc.), Nano-materials are widely used in the field of medicine, especially in targeted drug delivery, nano drug delivery systems, minimally invasive medicine and gene therapy and so on. In addition, in daily life, people often come into contact with substances containing nanomaterials.Typically, Nanomaterials enter human body through the respiratory, oral, mucosal, injection exposure modes. Then they are recognized by the immune system, internalized by phagocytic cells, inducing the interaction between nano-materials and the different components of the body’s immune system. There are large possibilities that the components of the immune system generate unexpected responses, thus interfering nanomaterials’ function that researchers have set at first. For example, when nanomaterials are used for targeted drug delivery, the immune response is not desired because nanomaterials can cause unexpected, adverse effect on the patient. In addition, the immune system is human body’s vital defense system maintaining its homeostasis, fending off the invading pathogens. The interaction mechanism between nanomaterial and immune system is top consideration in nanomaterials safety evaluation and expanding its applications.As a result, many researchers have turned to the subject of the interaction between nanoparticles and the immune system and started extensive investigation. However, results has shown that despite different surface properties of nanomaterials have certain impact on the human immune system, triggering multi-level immune responses. However, these nanomaterials are various in terms of a plurality of physical chemical properties, so it is blur to figure out the relationship between the sole nature of nanomaterials and its inflammation responses.Macrophages are an important part of the immune system, establishing the second channel with the humoral immune.Macrophages not only involve in innate immunity, also act as antigen presenting cells against foreign pathogens in adaptive immunity. Gold nanoparticles with relatively good biocompatibility, optical and electrical properties are distinct in various types of nanomaterials, which make it widely used in the biomedical field, and can be easily modified in the surface through different covalent bond. Thus, this paper select macrophage as representative of immune system to further explore the structure-activity relationship between surface physicochemical properties of nanomaterials and its immune response.This paper divided surface physicochemical properties of nanomaterials into surface charge density, hydrophilicity,π-π-conjugated density and steric hindrance. Through modulating the the ligands amount on the surface of the gold nanoparticles, we synthesized four gold nanoparticle arrays with four different continuous change surface physicochemical properties. Based on this platform, we explored the effect that these four GNP arrays on the macrophage TNF-a secretion via ELIS A method. Through these experiments, we can know that TNF-a secretion caused by four GNP arrays are a little lower than control group; π-π-conjugated density, steric hindrance and charge density did not cause TNF-a secretion change basically; TNF-a secretion increased with hydrophobicity. In addition, TNF-a secretion caused by π-π-conjugated density and steric hindrance GNP may be influenced by their hydrophobicity, at the same time, TNF-a secretion caused by charge GNP has nothing to with their hydrophobicity. The phenomenon that hydrophobic GNP induce more TNF-a secretion may coincide with the high cellular uptake amount in activating inflammation signal pathways.This research is vital in disclosing the potential immune toxicity and inflammation responses of gold nanoparticle, laying foundations for nano-bio interaction and provide certain reference in nanomaterial design.
Keywords/Search Tags:GNP arrays, macrophage, TNF-α
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