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一种用于癌症诊疗的新型纳米杂化物:叶酸敏化的FeO纳米颗粒用于结直肠癌诊断和光动力治疗。

A novel nanohybrid for cancer theranostics: folate sensitized FeO nanoparticles for colorectal cancer diagnosis and photodynamic therapy.

作者信息

Nandi Ramesh, Mishra Snehasis, Maji Tuhin Kumar, Manna Krishnendu, Kar Prasenjit, Banerjee Saswati, Dutta Shreyasi, Sharma S K, Lemmens Peter, Saha Krishna Das, Pal Samir Kumar

机构信息

Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India.

出版信息

J Mater Chem B. 2017 Jun 7;5(21):3927-3939. doi: 10.1039/c6tb03292c. Epub 2017 May 11.

DOI:10.1039/c6tb03292c
PMID:32264254
Abstract

Organic-inorganic nanohybrids are becoming popular for their potential biological applications, including diagnosis and treatment of cancerous cells. The motive of this study is to synthesise a nanohybrid for the diagnosis and therapy of colorectal cancer. Here we have developed a facile and cost-effective synthesis of folic acid (FA) templated FeO nanoparticles with excellent colloidal stability in water using a hydrothermal method for the theranostics applications. The attachment of FA to FeO was confirmed using various spectroscopic techniques including FTIR and picosecond resolved fluorescence studies. The nanohybrid (FA-FeO) is a combination of two nontoxic ingredients FA and FeO, showing remarkable photodynamic therapeutic (PDT) activity in human colorectal carcinoma cell lines (HCT 116) via generation of intracellular ROS. The light induced enhanced ROS activity of the nanohybrid causes significant nuclear DNA damage, as confirmed from the comet assay. Assessment of p53, Bax, Bcl2, cytochrome c (cyt c) protein expression and caspase 9/3 activity provides vivid evidence for cell death via an apoptotic pathway. In vitro magnetic resonance imaging (MRI) experiments in folate receptor (FR) overexpressed cancer cells (HCT 116) and FR deficient human embryonic kidney cells (HEK 293) reveal the target specificity of the nanohybrid towards cancer cells, and are thus pronounced MRI contrasting agents for the diagnosis of colorectal cancer.

摘要

有机-无机纳米杂化物因其潜在的生物应用,包括癌细胞的诊断和治疗,而越来越受欢迎。本研究的目的是合成一种用于结直肠癌诊断和治疗的纳米杂化物。在这里,我们开发了一种简便且经济高效的合成方法,使用水热法合成叶酸(FA)模板化的FeO纳米颗粒,该纳米颗粒在水中具有优异的胶体稳定性,可用于诊疗应用。通过包括傅里叶变换红外光谱(FTIR)和皮秒分辨荧光研究在内的各种光谱技术,证实了FA与FeO的结合。纳米杂化物(FA-FeO)是两种无毒成分FA和FeO的组合,通过产生细胞内活性氧(ROS),在人结肠癌细胞系(HCT 116)中显示出显著的光动力治疗(PDT)活性。彗星试验证实,纳米杂化物的光诱导增强ROS活性会导致显著的核DNA损伤。对p53、Bax、Bcl2、细胞色素c(cyt c)蛋白表达和半胱天冬酶9/3活性的评估为细胞通过凋亡途径死亡提供了确凿证据。在叶酸受体(FR)过表达的癌细胞(HCT 116)和FR缺陷的人胚肾细胞(HEK 293)中进行的体外磁共振成像(MRI)实验揭示了纳米杂化物对癌细胞的靶向特异性,因此是用于结直肠癌诊断的显著MRI造影剂。

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