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Cholesterol-coated gold nanorods as an efficient nano-carrier for chemotherapeutic delivery and potential treatment of breast cancer: in vitro studies using the MCF-7 cell line

机译:胆固醇包覆的金纳米棒可作为有效的纳米载体,用于化学治疗和乳腺癌的潜在治疗:使用MCF-7细胞系的体外研究

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Gold nanorods (GNRs) have a recognized role in treatment of cancers as efficient nanocarriers for chemotherapeutic drug delivery. In this study, GNRs modified with cholesterol-PEG were employed as a nanocarrier for a hydrophobic compound having a promising phosphatidylinositol 3-kinase (PI3Kα) inhibitory activity. The acquired nanocomplex was characterized by optical and infra-red (IR) absorption spectroscopies, in addition to hydrodynamic size and zeta potential. Glide docking and superposing of docked poses of the hydrophobic ligand and cholesterol moiety demonstrated that hydrophobic interactions drive the conjugation and attachment of the ligand to the cholesterol moiety of the nanocarrier. In vitro release study under a cellular environment indicates that the presence of cells has enhanced the release and the cellular uptake of the conjugated ligand. Furthermore, the anti-proliferative assay of the nanocomplex revealed potent cytotoxicity over a low concentration range of the nanocomplex against MCF-7 breast cancer cells compared to the free compound or the nanocarrier alone. Analysis of cellular death modality by flow cytometry showed that the nanocomplex has a rapid effect on cell death, as cells went toward the late apoptoticecrotic stage rapidly and proportionally to the increase of the nanocomplex concentration. The overall results propose that cholesterol-decorated GNRs could be considered as a promising nanocarrier for hydrophobic drugs to achieve efficient delivery and potential therapy against breast cancer cells.
机译:金纳米棒(GNRs)在癌症治疗中具有公认的作用,可作为有效的纳米载体用于化疗药物的输送。在这项研究中,胆固醇-PEG修饰的GNR被用作具有希望的磷脂酰肌醇3-激酶(PI3Kα)抑制活性的疏水化合物的纳米载体。除了流体动力学尺寸和ζ电位之外,所获得的纳米复合物还具有光学和红外(IR)吸收光谱学特征。滑动对接和疏水配体和胆固醇部分的对接姿势的叠加表明,疏水相互作用驱动配体与纳米载体的胆固醇部分的结合和附着。在细胞环境下的体外释放研究表明,细胞的存在增强了结合配体的释放和细胞吸收。此外,与单独的游离化合物或纳米载体相比,纳米复合物的抗增殖试验表明,在纳米复合物的低浓度范围内,它对MCF-7乳腺癌细胞具有强大的细胞毒性。通过流式细胞术对细胞死亡方式的分析表明,纳米复合物对细胞死亡具有快速的影响,因为细胞迅速并与纳米复合物浓度的增加成比例地进入凋亡/坏死后期。总体结果表明,胆固醇修饰的GNRs可以被视为疏水性药物的有前途的纳米载体,以实现有效的递送和对乳腺癌细胞的潜在治疗。

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