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用于潜在靶向抗癌药物递送、成像及作为磁共振成像造影剂的磁性纳米级金属有机框架

Magnetic nanoscale metal organic frameworks for potential targeted anticancer drug delivery, imaging and as an MRI contrast agent.

作者信息

Ray Chowdhuri Angshuman, Bhattacharya Dipsikha, Sahu Sumanta Kumar

机构信息

Department of Applied Chemistry, Indian School of Mines, Dhanbad 826 004, Jharkhand, India.

出版信息

Dalton Trans. 2016 Feb 21;45(7):2963-73. doi: 10.1039/c5dt03736k. Epub 2016 Jan 12.

Abstract

The development of a novel multifunctional porous nanoplatform for targeted anticancer drug delivery with cell imaging and magnetic resonance imaging has been realised in the current work. Here we have developed a magnetic nanoscale metal organic frameworks (NMOF) for potential targeted drug delivery. These magnetic NMOFs were fabricated by incorporation of Fe3O4 nanoparticles into porous isoreticular metal organic frameworks (IRMOF-3). To achieve targeted drug delivery towards cancer cells specifically, folic acid was conjugated to the NMOF surface. Then, the fluorescent molecule rhodamine B isothiocyanate (RITC) was conjugated to the NMOFs for biological imaging applications. The synthesized magnetic NMOFs were fully characterised by FTIR, powder XRD, XPS, SQUID, TGA, TEM, FESEM, and DLS. The synthesized magnetic NMOFs were observed to be smaller than 100 nm and were found to be nontoxic towards human cervix adenocarcinoma (HeLa) and murine fibroblast (NIH3T3) cells according to cell viability assays. The cancer chemotherapy drug paclitaxel was conjugated to the magnetic NMOFs through hydrophobic interactions with a relatively high loading capacity. Moreover, these folic acid-conjugated magnetic NMOFs showed stronger T2-weighted MRI contrast towards the cancer cells, justifying their possible significance in imaging.

摘要

在当前的工作中,已实现了一种用于靶向抗癌药物递送并兼具细胞成像和磁共振成像功能的新型多功能多孔纳米平台的开发。在此,我们开发了一种用于潜在靶向药物递送的磁性纳米级金属有机框架(NMOF)。这些磁性NMOF是通过将Fe3O4纳米颗粒掺入多孔同网状金属有机框架(IRMOF - 3)中制备而成。为了实现对癌细胞的特异性靶向药物递送,将叶酸缀合到NMOF表面。然后,将荧光分子异硫氰酸罗丹明B(RITC)缀合到NMOF上用于生物成像应用。通过傅里叶变换红外光谱(FTIR)、粉末X射线衍射(XRD)、X射线光电子能谱(XPS)、超导量子干涉仪(SQUID)、热重分析(TGA)、透射电子显微镜(TEM)、场发射扫描电子显微镜(FESEM)和动态光散射(DLS)对合成的磁性NMOF进行了全面表征。观察到合成的磁性NMOF小于100 nm,并且根据细胞活力测定发现其对人宫颈腺癌(HeLa)和小鼠成纤维细胞(NIH3T3)无毒。癌症化疗药物紫杉醇通过疏水相互作用以相对较高的负载量缀合到磁性NMOF上。此外,这些叶酸缀合的磁性NMOF对癌细胞表现出更强的T2加权磁共振成像对比度,证明了它们在成像方面可能具有的重要意义。

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