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基于磁小体的药物偶联物用于癌症治疗的制备及表征。

Preparation and characterisation of magnetosomes based drug conjugates for cancer therapy.

机构信息

Marine Biotechnology and Bioproducts Laboratory, School of Biosciences and Technology, Vellore Institute of Technology, Vellore-632014, Tamilnadu, India.

出版信息

IET Nanobiotechnol. 2020 Dec;14(9):815-822. doi: 10.1049/iet-nbt.2020.0082.

Abstract

The authors report a novel, effective and enhanced method of conjugating anticancer drug, paclitaxel and gallic acid with magnetosomes. Here, anticancer drugs were functionalised with magnetosomes membrane by direct and indirect (via crosslinkers: glutaraldehyde and 3-aminopropyltriethoxysilane) adsorption methods. The prepared magnetosome-drug conjugates were characterised by Fourier transform infrared, zeta potential, field-emission scanning electron microscope and thermogravimetric analysis/differential scanning calorimetry. The drug-loading efficiency and capacity were found to be 87.874% for paclitaxel (MP) and 71.3% for gallic acid (MG), respectively as calculated by ultraviolet spectroscopy and high-performance liquid chromatography. The drug release demonstrated by the diffusion method in phosphate buffer (PBS), showing a prolonged drug release for MP and MG, respectively. The cytotoxicity effect of the MP and MG displayed cytotoxicity of 69.71%, 55.194% against HeLa and MCF-7 cell lines, respectively. The reactive oxygen species, acridine orange and ethidium bromide and 4, 6-diamidino-2-phenylindole staining of the drug conjugates revealed the apoptotic effect of MP and MG. Further, the regulation of tumour suppressor protein, p53 was determined by western blotting which showed an upregulation of p53. Comparatively, the magnetosome-drug conjugates prepared by direct adsorption achieved the best effects on the drug-loading efficiency and the increased percentage of cancer cell mortality and the upregulation of P53. The proposed research ascertains that magnetosomes could be used as effective nanocarriers in cancer therapy.

摘要

作者报道了一种新颖、有效且增强的将抗癌药物紫杉醇和没食子酸与磁小体偶联的方法。在此,通过直接(通过交联剂:戊二醛和 3-氨基丙基三乙氧基硅烷)和间接(通过交联剂:戊二醛和 3-氨基丙基三乙氧基硅烷)吸附方法将抗癌药物功能化到磁小体膜上。通过傅里叶变换红外光谱、ζ 电位、场发射扫描电子显微镜和热重分析/差示扫描量热法对制备的磁小体-药物偶联物进行了表征。通过紫外光谱法和高效液相色谱法计算,紫杉醇(MP)和没食子酸(MG)的载药效率和载药能力分别为 87.874%和 71.3%。通过扩散法在磷酸盐缓冲液(PBS)中进行的药物释放显示,MP 和 MG 分别表现出延长的药物释放。MP 和 MG 的细胞毒性作用对 HeLa 和 MCF-7 细胞系的细胞毒性分别为 69.71%和 55.194%。吖啶橙和溴化乙锭以及 4,6-二脒基-2-苯基吲哚染色的药物偶联物显示了 MP 和 MG 的凋亡作用。此外,通过蛋白质印迹法测定肿瘤抑制蛋白 p53 的表达水平,结果表明 p53 上调。相比之下,通过直接吸附法制备的磁小体-药物偶联物在载药效率和增加癌细胞死亡率百分比以及上调 P53 方面取得了最佳效果。该研究证实,磁小体可用作癌症治疗中的有效纳米载体。

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