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载药靶向 MUC-1 适体的金修饰超顺磁性氧化铁纳米颗粒用于结肠癌的磁共振成像与光热治疗。

Theranostic MUC-1 aptamer targeted gold coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging and photothermal therapy of colon cancer.

机构信息

Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.

Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm, Sweden.

出版信息

Colloids Surf B Biointerfaces. 2016 Jul 1;143:224-232. doi: 10.1016/j.colsurfb.2016.02.058. Epub 2016 Feb 27.

Abstract

Favorable physiochemical properties and the capability to accommodate targeting moieties make superparamegnetic iron oxide nanoparticles (SPIONs) popular theranostic agents. In this study, we engineered SPIONs for magnetic resonance imaging (MRI) and photothermal therapy of colon cancer cells. SPIONs were synthesized by microemulsion method and were then coated with gold to reduce their cytotoxicity and to confer photothermal capabilities. Subsequently, the NPs were conjugated with thiol modified MUC-1 aptamers. The resulting NPs were spherical, monodisperse and about 19nm in size, as shown by differential light scattering (DLS) and transmission electron microscopy (TEM). UV and X-ray photoelectron spectroscopy (XPS) confirmed the successful gold coating. MTT results showed that Au@SPIONs have insignificant cytotoxicity at the concentration range of 10-100μg/ml (P>0.05) and that NPs covered with protein corona exerted lower cytotoxicity than bare NPs. Furthermore, confocal microscopy confirmed the higher uptake of aptamer-Au@SPIONs in comparison with non-targeted SPIONs. MR imaging revealed that SPIONs produced significant contrast enhancement in vitro and they could be exploited as contrast agents. Finally, cells treated with aptamer-Au@SPIONs exhibited a higher death rate compared to control cells upon exposure to near infrared light (NIR). In conclusion, MUC1-aptamer targeted Au@SPIONs could serve as promising theranostic agents for simultaneous MR imaging and photothermal therapy of cancer cells.

摘要

具有良好的理化性质和容纳靶向分子的能力,使超顺磁性氧化铁纳米粒子(SPIONs)成为热门的治疗诊断一体化试剂。在本研究中,我们设计了用于磁共振成像(MRI)和结肠癌细胞光热治疗的 SPIONs。SPIONs 通过微乳液法合成,然后用金包覆以降低其细胞毒性并赋予光热能力。随后,将 NPs 与巯基修饰的 MUC-1 适体偶联。所得 NPs 为球形、单分散的,大小约为 19nm,如差示光散射(DLS)和透射电子显微镜(TEM)所示。UV 和 X 射线光电子能谱(XPS)证实了成功的金包覆。MTT 结果表明,Au@SPIONs 在 10-100μg/ml 的浓度范围内具有不显著的细胞毒性(P>0.05),并且带有蛋白冠的 NPs 比裸 NPs 具有更低的细胞毒性。此外,共聚焦显微镜证实了与非靶向 SPIONs 相比,适配体-Au@SPIONs 的摄取量更高。MR 成像显示 SPIONs 在体外产生了显著的对比增强,可将其用作对比剂。最后,与对照细胞相比,用适配体-Au@SPIONs 处理的细胞在近红外光(NIR)照射下表现出更高的死亡率。总之,MUC1-aptamer 靶向的 Au@SPIONs 可作为同时进行磁共振成像和光热治疗癌症细胞的有前途的治疗诊断一体化试剂。

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