Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres.
Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres.
复制标题
由姜黄素加载的自组装富集精氨酸RGD纳米球诱导的MG-63骨肉瘤细胞增殖的选择性抑制。
DOI：
10.2147/ijn.s78756
复制
发表时间：
2015
影响因子：
8
通讯作者：
Webster TJ
中科院分区：
文献类型：
--
作者：
Chang R;Sun L;Webster TJ
骨肉瘤是骨癌最常见的原发恶性形式，占所有骨癌病例的30%。这项体外研究的目的是开发一种对骨肉瘤细胞具有较高选择性，对正常健康成骨细胞具有较低细胞毒性的抗骨肉瘤药物。姜黄素(或二阿魏酰甲烷)通过多种细胞途径被发现具有抗氧化和抗癌作用。但在碱性条件下，其水溶性较低，降解率较高。本研究以两亲性多肽C18GR7RGDS作为姜黄素的水溶液载体。该肽含有一个疏水的脂肪族尾基，通过疏水相互作用进行自组装，以及一个由富含精氨酸和精氨酸-甘氨酸-天冬氨酸结构组成的亲水性头基。通过透射电子显微镜表征，观察到直径为10~20 nm的球形两亲纳米粒子(APNPs)在水和磷酸盐缓冲溶液中的自组装结构，但当pH值降至4时，这种结构解离。采用与醋酸共溶解和透析管的方法，提高了姜黄素的溶解度，并在APNPs存在下形成了均一的溶液。通过傅立叶变换红外光谱和X-射线衍射仪分析，证实姜黄素在APNPs中得到了成功的包裹。用四甲基偶氮唑蓝比色法和共聚焦荧光显微镜检测APNP/姜黄素复合体对骨肉瘤和正常成骨细胞系的细胞毒性和细胞摄取。结果表明，与正常成骨细胞相比，载姜黄素的APNPs对MG-63骨肉瘤细胞具有明显的选择性杀伤作用。我们首次证明了APNPs可以将疏水的姜黄素包裹在其疏水的核心中，并且载姜黄素的APNPs可以成为一种选择性抑制骨肉瘤细胞的创新治疗方法。
Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane) has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs) with diameters of 10–20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective cytotoxicity against MG-63 osteosarcoma cells when compared with normal osteoblasts. We have demonstrated for the first time that APNPs can encapsulate hydrophobic curcumin in their hydrophobic cores, and curcumin-loaded APNPs could be an innovative treatment for the selective inhibition of osteosarcoma cells.