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Highly branched amine-functionalized p-sulfonatocalix[4]arene decorated with human plasma proteins as a smart, targeted, and stealthy nano-vehicle for the combination chemotherapy of MCF7 cells
New Journal of Chemistry ( IF 3.3 ) Pub Date : 2018-06-22 00:00:00 , DOI: 10.1039/c8nj01790e
Mahdi Rahimi 1, 2, 3, 4, 5 , Ramin Karimian 5, 6, 7, 8, 9 , Elmira Mostafidi 5, 10, 11, 12 , Ehsan Bahojb Noruzi 2, 3, 5, 12, 13 , Sepehr Taghizadeh 5, 11, 12, 14 , Behrooz Shokouhi 5, 10, 11, 12 , Hossein Samadi Kafil 5, 11, 12, 15
Affiliation  

Nanotechnology has recently emerged as a promising field for biomedical applications, especially the targeted delivery of drugs to tumors. Besides, combination chemotherapy is common in cancer treatment and is rapidly evolving. Therefore, the successfully delivery of chemotherapeutic drugs to targeted cancers is a big challenge. In this study, we endeavour to develop a nano-vehicle, based on highly branched amine-functionalized p-sulfonatocalix[4]arene, to act as a dual-drug carrier for the co-delivery of DOX and MTX to MCF7 breast cancer cells with targeting and synergistic effects. After the synthesis and preparation of the nano-vehicle, structural characterization was also conducted (FTIR, AFM, VSM, SEM, EDX, XRD, DLS, and zeta potential analyses). Drug loading and release studies on the prepared drug-loaded nano-vehicle were conducted to optimize the formulation. The designed platform has targeting and pH-triggered drug release capabilities to improve the therapeutic index of DOX and MTX. Hemolysis assay results proved that the nano-vehicle has high blood compatibility, even for high dosage treatment. The protein–particle interactions of the nano-vehicle in human blood circulation systems were simulated via SDS-PAGE assays and the results indicated that a series of proteins were attached to the surface of the nano-vehicle. This feature gives the nano-vehicle stealth properties in the blood circulation system. The cellular uptake, from flow-cytometry and fluorescence microscopy, validated that the human plasma proteins attached to the nano-vehicle surface gave the nano-vehicle high internalization capabilities into cells due to the presence of some protein receptors on the surfaces of cancer cells, improving the tumor cell targeting properties. MTT assays and DAPI staining were also performed to show the viability and DNA fragmentation of treated cells. All results validated one another and confirmed that our designed nano-vehicle is useful for targeted and combination drug delivery systems with stealth properties.

中文翻译:

高度支化的胺官能化的p -sulfonatocalix [4]芳烃与人血浆蛋白的装饰为智能,定位和隐蔽的纳米车辆MCF7细胞的联合化疗

纳米技术近来已经成为生物医学应用的有前途的领域,尤其是靶向药物向肿瘤的递送。此外,联合化疗在癌症治疗中很普遍,并且正在迅速发展。因此,成功地将化学治疗药物递送至靶向的癌症是一个巨大的挑战。在这项研究中,我们努力开发一种基于高度支化胺官能化p的纳米车辆-sulfonatocalix [4] arene,用作双重药物载体,可将DOX和MTX共同递送至MCF7乳腺癌细胞,并具有靶向作用和协同作用。在合成和制备纳米载体之后,还进行了结构表征(FTIR,AFM,VSM,SEM,EDX,XRD,DLS和ζ电位分析)。在制备的载有药物的纳米载体上进行了载药和释放研究,以优化配方。设计的平台具有针对性和pH触发的药物释放功能,可提高DOX和MTX的治疗指数。溶血测定结果证明,即使用于高剂量治疗,纳米车辆也具有高血液相容性。纳米载体在人类血液循环系统中的蛋白质-颗粒相互作用是通过以下方式模拟的SDS-PAGE分析和结果表明,一系列蛋白质附着在纳米载体的表面。此功能赋予了血液循环系统中的纳米车辆隐形性能。流式细胞仪和荧光显微镜对细胞的摄取证实,由于癌细胞表面上存在某些蛋白质受体,附着在纳米载体表面的人类血浆蛋白使纳米载体具有高度的内在化进入细胞的能力,改善肿瘤细胞的靶向特性。还进行了MTT分析和DAPI染色以显示处理过的细胞的活力和DNA片段化。所有结果都相互验证,并确认我们设计的纳米车辆可用于具有隐身特性的靶向和组合药物输送系统。
更新日期:2018-06-22
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