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用于生物医学应用的生物相容性ι-卡拉胶-γ-磁赤铁矿纳米复合材料——合成、表征及体外抗癌疗效

Biocompatible ι-carrageenan-γ-maghemite nanocomposite for biomedical applications - synthesis, characterization and in vitro anticancer efficacy.

作者信息

Raman Maya, Devi Viswambari, Doble Mukesh

机构信息

Bioengineering and Drug design Lab, Department of Biotechnology, IIT-Madras, Chennai, 600036, India.

出版信息

J Nanobiotechnology. 2015 Mar 3;13:18. doi: 10.1186/s12951-015-0079-3.

Abstract

BACKGROUND

Carrageenans are naturally occurring hydrophilic, polyanionic polysaccharide bioploymers with wide application in pharmaceutical industries for controlled drug delivery. Magnetic nanoparticles with their exceptional properties enable them to be an ideal candidate for the production of functional nanostructures, thus facilitating them for biomedical applications. The development of novel nanocomposite by coupling the synergistic effects of the sulfated polysaccharide (iota carrageenan) and a magnetic nanoparticle (maghemite) may offer new interesting applications in drug delivery and cancer therapy. The nanocomposite was characterized by ultraviolet-visible spectroscopy, high resolution scanning electron microscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy and powder XRD to highlight the possible interaction between the two components. Biocompatibility and the anticancer efficacy of the nanocomposite were assayed and analysed in vitro.

RESULTS

Results suggested that iota carrageenans have electrostatically entrapped the maghemite nanoparticles in their sulfate groups. Biocompatibility of the nanocomposite (at different concentrations) against normal cell lines (HEK-293 and L6) was confirmed by MTT assay. Hoechst 33342 and 7-AAD staining studies under fluorescent microscopy revealed that the nanocomposite is able to induce appoptosis as the mode of cell death in human colon cancer cell line (HCT116). Cell apoptosis here is induced by following the ROS-mediated mitochondrial pathway, combined with downregulation of the expression levels of mRNA of XIAP and PARP-1 and upregulation of caspase3, Bcl-2 and Bcl-xL.

CONCLUSIONS

This novel nanocomposite is biocompatible with potential properties to serve in magnet aided targeted drug delivery and cancer therapy.

摘要

背景

角叉菜胶是天然存在的亲水性、聚阴离子多糖生物聚合物,在制药行业的控释药物递送中有着广泛应用。磁性纳米颗粒因其优异性能使其成为生产功能性纳米结构的理想候选材料,从而促进其在生物医学领域的应用。通过耦合硫酸化多糖(ι-角叉菜胶)和磁性纳米颗粒(磁赤铁矿)的协同效应来开发新型纳米复合材料,可能会在药物递送和癌症治疗方面带来新的有趣应用。通过紫外可见光谱、高分辨率扫描电子显微镜、动态光散射分析、傅里叶变换红外光谱和粉末X射线衍射对该纳米复合材料进行表征,以突出两种成分之间可能的相互作用。在体外测定并分析了该纳米复合材料的生物相容性和抗癌功效。

结果

结果表明,ι-角叉菜胶已通过其硫酸根基团静电捕获了磁赤铁矿纳米颗粒。通过MTT法证实了该纳米复合材料(在不同浓度下)对正常细胞系(HEK-293和L6)的生物相容性。荧光显微镜下的Hoechst 33342和7-AAD染色研究表明,该纳米复合材料能够诱导人结肠癌细胞系(HCT116)发生细胞凋亡,作为细胞死亡的方式。此处细胞凋亡是通过ROS介导的线粒体途径诱导的,同时伴随着XIAP和PARP-1 mRNA表达水平的下调以及caspase3、Bcl-2和Bcl-xL的上调。

结论

这种新型纳米复合材料具有生物相容性,具有在磁辅助靶向药物递送和癌症治疗中发挥作用的潜在特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ff/4356133/ce8d9c5ddf6a/12951_2015_79_Fig1_HTML.jpg

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