Synthesis and Evaluation of Nano-antioxidants for Medical Applications

医用纳米抗氧化剂的合成与评价

• 批准号: 7934174
• 负责人: Choon Young Lee
• 金额: $ 5.79万
• 依托单位: CENTRAL MICHIGAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934174
• 关键词: Agar Gel Electrophoresis; Antioxidants; Architecture; Area; Arthritis; Ascorbic Acid; Atherosclerosis; Biological; Biological Assay; Cardiovascular Diseases; Cardiovascular system; Cations; Cells; Chemicals; Chronic; DNA; Data; Dendrimers; Detection; Diagnosis; Disease; Electron Spin Resonance Spectroscopy; Environment; Erythrocytes; Evaluation; Exhibits; Fluorescence Spectroscopy; Free Radical Scavenging; Free Radicals; Hand; Health; Hemolysis; High Pressure Liquid Chromatography; Human; Hydrochloride Salt; Hydrogen; Hydrogen Bonding; Immune system; In Vitro; Inflammatory; Lead; Light; Lipid Peroxidation; Lipids; Lung; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Medical; Molecular; Molecular Sieve Chromatography; Molecular Weight; Monitor; Nanotechnology; Natural regeneration; Nature; Nerve Degeneration; Neurodegenerative Disorders; Outcome; Oxidative Stress; Oxygen; Pathogenesis; Phase; Polyacrylamide Gel Electrophoresis; Polymers; Porifera; Prevention; Production; Property; Proteins; Pulmonary Hypertension; Reperfusion Injury; Reporting; Research; Role; Solubility; Spectrum Analysis; Structure; Sulfonic Acids; Surface; System; Techniques; Trees; Ultraviolet Spectrophotometry; Water; Work; analytical method; aqueous; ascorbate; cell injury; diene; gel electrophoresis; human disease; improved; interest; nano; nanodevice; nanomaterials; nanoparticle; novel; prevent; propargylamine; protective effect; public health relevance; small molecule

DESCRIPTION (provided by applicant): Antioxidants have been reported to be beneficial for prevention of a variety of human diseases including cancer and cardiovascular, neurodegenerative, pulmonary and chronic ailments. Commonly available antioxidants are small molecular weight compounds that have the ability to neutralize free radicals, destroy potential radical forming substances, boost the immune system and exhibit other biological activities that are beneficial to human health. Little is known about large antioxidant molecules with molecular weights in the thousands. More specifically, the biological effects of dendritic forms of antioxidants have not been reported before. This application involves the synthesis of antioxidant dendrimers composed of numerous units of antioxidants connected to one another in a tree like fashion so that they can effectively scavenge free radicals. The nano-antioxidant molecules will be synthesized with dihydroxybenzaldehyde building blocks and propargylamine branching units in a reiterative manner to give well-defined and precise dendrimers. It is hypothesized that this unique antioxidant architecture will display cooperative effects and reveal some interesting and beneficial properties such as improved aqueous solubility and stability and enhanced radical scavenging potency. It is also believed that these nano-particles will have stronger interactions with biomolecules and therefore be better protectants than small molecule antioxidants against free radical damage. These novel nano-materials will be characterized by a number of chemical and bio-analytical techniques including polyacrylamide gel electrophoresis, HPLC, spectroscopy and mass spectrometry. Their antioxidant potency will be measured with electron spin resonance and spectroscopic assays and compared to controls, such as their monomeric counterparts (building block) and common antioxidants like vitamins C and E. The ability of the antioxidant dendrimers to protect DNA, lipids, proteins and red blood cells will be determined in a free radical generating system in vitro and compared to small molecule antioxidants. DNA strand breakage will be determined by agarose gel electrophoresis. Protein damage will be monitored by fluorescence spectroscopy, reversed phase HPLC, size exclusion chromatography, and gel electrophoresis. Lipid peroxidation will be measured by monitoring diene formation with ultraviolet spectrophotometry while cell damage will be evaluated by red blood cell hemolysis. These studies should provide invaluable data towards the protective effects of nano-antioxidants on biomolecules and cells. In addition, the proposed antioxidant dendrimer will provide a unique platform for preparing multifunctional nano-devices for detection, diagnosis and treatment of diseases. PUBLIC HEALTH RELEVANCE: This application will involve the synthesis of antioxidant dendrimers and investigate their free radical scavenging potency as well as their effects on biomolecules and cells. Results of this study will benefit the use of nano-antioxidants for prevention, detection, diagnosis and treatment of human diseases that have a strong association with oxidative stress including cancer, cardiovascular diseases, and chronic inflammatory and neurodegenerative diseases.

描述（由申请人提供）：据报道，抗氧化剂有益于预防多种人类疾病，包括癌症和心血管疾病、神经变性疾病、肺部疾病和慢性疾病。通常可用的抗氧化剂是小分子量化合物，其具有中和自由基、破坏潜在的自由基形成物质、增强免疫系统并表现出有益于人类健康的其他生物活性的能力。人们对分子量在数千的大抗氧化剂分子知之甚少。更具体地说，树突状形式的抗氧化剂的生物学效应以前没有报道过。该应用涉及抗氧化剂树状聚合物的合成，所述抗氧化剂树状聚合物由以树状方式彼此连接的许多抗氧化剂单元组成，使得它们可以有效地抑制自由基。纳米抗氧化剂分子将与二羟基苯甲醛构建块和炔丙胺分支单元以迭代方式合成，以得到定义明确且精确的树枝状聚合物。据推测，这种独特的抗氧化剂结构将显示协同效应，并揭示一些有趣的和有益的特性，如改善的水溶性和稳定性和增强的自由基清除效力。人们还认为，这些纳米颗粒将与生物分子具有更强的相互作用，因此比小分子抗氧化剂更好地保护自由基损伤。这些新的纳米材料将通过许多化学和生物分析技术来表征，包括聚丙烯酰胺凝胶电泳、HPLC、光谱和质谱。它们的抗氧化效力将通过电子自旋共振和光谱分析进行测量，并与对照品进行比较，例如它们的单体对应物（构建块）和常见的抗氧化剂，如维生素C和E。抗氧化剂树枝状聚合物保护DNA、脂质、蛋白质和红细胞的能力将在体外自由基生成系统中测定，并与小分子抗氧化剂进行比较。将通过琼脂糖凝胶电泳测定DNA链断裂。将通过荧光光谱、反相HPLC、分子排阻色谱和凝胶电泳监测蛋白质损伤。将通过紫外分光光度法监测二烯形成来测量脂质过氧化，同时通过红细胞溶血来评价细胞损伤。这些研究将为纳米抗氧化剂对生物分子和细胞的保护作用提供宝贵的数据。此外，所提出的抗氧化剂树状聚合物将为制备用于检测、诊断和治疗疾病的多功能纳米器件提供独特的平台。公共卫生相关性：该应用将涉及抗氧化剂树枝状聚合物的合成，并研究其自由基清除能力以及对生物分子和细胞的影响。这项研究的结果将有利于使用纳米抗氧化剂预防，检测，诊断和治疗与氧化应激有密切关系的人类疾病，包括癌症，心血管疾病，慢性炎症和神经退行性疾病。