Nday Christiane M, Halevas Eleftherios, Jackson Graham E, Salifoglou Athanasios
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Department of Chemistry, University of Cape Town, Rondebosch 7700, Cape Town, South Africa.
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
J Inorg Biochem. 2015 Apr;145:51-64. doi: 10.1016/j.jinorgbio.2015.01.001. Epub 2015 Jan 10.
Neurodegenerative diseases entail deeply complex processes, intimately associated with progressive brain damage reflecting cellular demise. Biochemical reactivity linked to such processes in Alzheimer's disease involves, among others, metal-induced oxidative stress contributing to neuronal cell death. Prominent among redox active metals inducing oxidative stress is Cu(II). Poised to develop molecular technology counteracting oxidative stress, efforts were launched to prepare bioactive hybrid nanoparticles, capable of working as host-carriers of potent antioxidants, such as the natural flavonoid quercetin. Employing synthetic protocols consistent with the assembly of silica nanoparticles, PEGylated and CTAB-modified materials were synthesized. Subsequent concentration-dependent loading of quercetin led to well-defined molecular carriers, the antioxidant efficiency of which was determined through drug release studies using UV-visible spectroscopy. The physicochemical characterization (elemental analysis, particle size, z-potential, FT-IR, thermogravimetric analysis, scanning electron microscopy) of the empty and loaded silica nanoparticles led to the formulation of optimized material linked to the delivery of the encapsulated antioxidant to primary rat hippocampal cultures under oxidative stress. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles as far as the loading capacity in quercetin (concentration dependence), b) congruence with the physicochemical features determined, and c) the release profile of the nanoparticle load under oxidative stress in neuronal cultures. The bio-activity profile of quercetin nanoparticles in a neurodegenerative environment brought on by Cu(II) a) denotes the improved specificity of antioxidant reactivity counteracting oxidative stress, and b) sets the stage for the development of molecular protection and preventive medical nanotechnology of relevance to neurodegenerative Alzheimer's disease.
神经退行性疾病涉及极其复杂的过程，与反映细胞死亡的进行性脑损伤密切相关。在阿尔茨海默病中，与此类过程相关的生化反应尤其涉及金属诱导的氧化应激，这会导致神经元细胞死亡。在诱导氧化应激的氧化还原活性金属中，铜（II）最为突出。为了开发对抗氧化应激的分子技术，人们努力制备生物活性杂化纳米颗粒，使其能够作为强力抗氧化剂（如天然黄酮类化合物槲皮素）的宿主载体。采用与二氧化硅纳米颗粒组装一致的合成方案，合成了聚乙二醇化和十六烷基三甲基溴化铵修饰的材料。随后槲皮素的浓度依赖性负载产生了明确的分子载体，其抗氧化效率通过使用紫外可见光谱的药物释放研究来确定。对空的和负载的二氧化硅纳米颗粒进行的物理化学表征（元素分析、粒径、ζ电位、傅里叶变换红外光谱、热重分析、扫描电子显微镜）导致了优化材料的配方，该材料与在氧化应激下将封装的抗氧化剂递送至原代大鼠海马体培养物有关。包封和药物释放研究表明：a）杂化纳米颗粒在槲皮素负载能力方面（浓度依赖性）的能力；b）与所确定的物理化学特征相符；c）在神经元培养物中氧化应激下纳米颗粒负载的释放曲线。槲皮素纳米颗粒在由铜（II）引发的神经退行性环境中的生物活性概况：a）表明抗氧化反应对抗氧化应激的特异性提高；b）为与神经退行性阿尔茨海默病相关的分子保护和预防性医学纳米技术的发展奠定了基础。
