Synthesis and Characterization of Curcumin Gold Nanoparticles: Sonosensitizer Agent for Atherosclerosis

RAN Pub Date : 2016-04-01 DOI:10.11159/NDDTE16.115
T. Henrique, C. Alencar, B. Luis, Lilia Coronato Courrol
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Abstract

Extended Abstract Atherosclerosis is a chronic inflammatory disease and the primary cause of human death worldwide[1]. Some studies have suggested that macrophages play a critical role in the development, progression, and destabilization of atherosclerotic plaques[2]. Thus, the reduction of macrophages from plaques represents a new strategy for the treatment of atherosclerosis[3]. Sonodynamic therapy (SDT) is emerging as a new atherosclerosis treatment[4] due to the generation of free radicals by activated sonosensitizers, which can lead to apoptotic cell death. The use of gold nanoparticles (AuNPs) as the vehicle for a sensitizer delivery improves reactive oxygen species formation [5]. Curcumin (Curc), a polyphenol derived from the Curcuma Longa plant, presents a sonodynamic effect on THP-1 derived macrophages [3]. The aim of this present study is to evaluate the effects of SDT on the viability of THP-1 macrophages incubated with Curc:AuNPs. To prepare Curcumin Gold Nanoparticles (Curc:AuNps) solutions, 3.2 mg of chloroauric acid was mixed with 1.5 mg of Curcumin and Polyethylene glycol (PEG) in Mili-Q water. The synthesized nanoparticles were characterized by UV/Vis optical absorption, and electron microscopy. THP-1 macrophages were incubated with Curc and Curc:AuNPs for 2 hours and then exposed to pulsed ultrasound irradiation (2 W/cm with 1.0 MHz ) for 5, 10 and 15 min. The survival rate of the cells was measured by MTT assay. All quantitative results were obtained from at least triplicate samples. The successful synthesis of the Curc:AuNps was indicated by the presence of a surface plasmon resonance at ~520 nm, characteristic of spherical gold nanoparticles. TEM analyses showed ~17±2 nm nanoparticles. The Curc:AuNPs SDT decreased cell viability more significantly than the treatment with ultrasound alone, mainly in cells treated for 15 min. Treatment with curcumin alone did not affect the cell viability when compared to control. The findings suggested that Curc:AuNps under low-intensity ultrasound has sonodynamic effect on THP-1 macrophages via generation of intracellular singlet oxygen and photothermic effect, indicating that Curc:AuNps can be used as a novel sonosensitizer in SDT for atherosclerosis. This work was supported by the “Fundacao de Amparo a Pesquisa do Estado de Sao Paulo” (FAPESP), Grant number 2014/06960-9.
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姜黄素金纳米颗粒:动脉粥样硬化超声增敏剂的合成与表征
动脉粥样硬化是一种慢性炎症性疾病,是世界范围内人类死亡的主要原因。一些研究表明,巨噬细胞在动脉粥样硬化斑块[2]的发生、进展和不稳定中起着关键作用。因此,从斑块中减少巨噬细胞代表了一种治疗动脉粥样硬化[3]的新策略。声动力疗法(SDT)正在成为一种新的动脉粥样硬化治疗方法,因为激活的声敏剂会产生自由基,导致细胞凋亡。使用金纳米颗粒(AuNPs)作为敏化剂递送的载体可以改善活性氧的形成[5]。姜黄素(Curc)是一种从姜黄植物中提取的多酚,对THP-1衍生的巨噬细胞[3]具有声动力作用。本研究的目的是评估SDT对Curc:AuNPs孵育的THP-1巨噬细胞活力的影响。将3.2 mg氯金酸与1.5 mg姜黄素和聚乙二醇(PEG)在Mili-Q水中混合,制备姜黄素金纳米颗粒(Curc:AuNps)溶液。通过紫外/可见光吸收和电子显微镜对合成的纳米颗粒进行了表征。将THP-1巨噬细胞与Curc和Curc:AuNPs孵育2小时后,分别于脉冲超声(2 W/cm, 1.0 MHz)照射5、10和15分钟,采用MTT法测定细胞存活率。所有定量结果均来自至少三个重复的样品。Curc:AuNps的成功合成表明,在~520 nm存在表面等离子体共振,这是球形金纳米颗粒的特征。TEM分析显示~17±2 nm的纳米颗粒。结果表明:与超声单独治疗相比,AuNPs SDT更显著地降低了细胞活力,主要是在治疗15分钟的细胞中。与对照组相比,姜黄素单独治疗不影响细胞活力。研究结果表明,低强度超声作用下Curc:AuNps通过产生细胞内单线态氧和光热效应对THP-1巨噬细胞产生声动力作用,表明Curc:AuNps可作为一种新型的超声增敏剂用于动脉粥样硬化SDT治疗。这项工作得到了“圣保罗州和平与发展基金”(FAPESP)的资助,资助号2014/06960-9。
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