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将6-姜酚、阿霉素和海藻酸羟基磷灰石制成生物相容性制剂:增强对乳腺癌和肝癌细胞的抗增殖作用。

Fabrication of 6-gingerol, doxorubicin and alginate hydroxyapatite into a bio-compatible formulation: enhanced anti-proliferative effect on breast and liver cancer cells.

作者信息

Manatunga Danushika C, de Silva Rohini M, de Silva K M Nalin, Wijeratne Dulharie T, Malavige Gathsaurie Neelika, Williams Gareth

机构信息

Department of Chemistry, University of Colombo, Colombo, 00300, Sri Lanka.

Sri Lanka Institute of Nanotechnology (SLINTEC), Nanotechnology & Science Park, Mahenwatte, Pitipana, Homagama, 10206, Sri Lanka.

出版信息

Chem Cent J. 2018 Nov 23;12(1):119. doi: 10.1186/s13065-018-0482-6.

Abstract

Ample attention has been devoted to the construction of anti-cancer drug delivery systems with increased stability, and controlled and targeted delivery, minimizing toxic effects. In this study we have designed a magnetically attractive hydroxyapatite (m-HAP) based alginate polymer bound nanocarrier to perform targeted, controlled and pH sensitive drug release of 6-gingerol, doxorubicin, and their combination, preferably at low pH environments (pH 5.3). They have exhibited higher encapsulation efficiency which is in the range of 97.4-98.9% for both 6-gingerol and doxorubicin molecules whereas the co-loading has accounted for a value of 81.87 ± 0.32%. Cell proliferation assays, fluorescence imaging and flow cytometric analysis, demonstrated the remarkable time and dose responsive anti-proliferative effect of drug loaded nanoparticles on MCF-7 cells and HEpG2 cells compared with their neat counter parts. Also, these systems have exhibited significantly reduced toxic effects on non-targeted, non-cancerous cells in contrast to the excellent ability to selectively kill cancerous cells. This study has suggested that this HAP based system is a versatile carrier capable of loading various drug molecules, ultimately producing a profound anti-proliferative effect.

摘要

人们对构建具有更高稳定性、可控和靶向递送功能且能将毒性作用降至最低的抗癌药物递送系统给予了充分关注。在本研究中,我们设计了一种基于磁性吸引的羟基磷灰石(m-HAP)的藻酸盐聚合物结合纳米载体,以实现6-姜酚、阿霉素及其组合药物在低pH环境(pH 5.3)下的靶向、可控和pH敏感药物释放。它们表现出较高的包封效率,6-姜酚和阿霉素分子的包封效率均在97.4 - 98.9%范围内,而共负载率为81.87±0.32%。细胞增殖试验、荧光成像和流式细胞术分析表明,与未负载药物的对应物相比,负载药物的纳米颗粒对MCF-7细胞和HEpG2细胞具有显著的时间和剂量响应性抗增殖作用。此外,与选择性杀死癌细胞的卓越能力形成对比的是,这些系统对非靶向、非癌细胞的毒性作用显著降低。本研究表明,这种基于HAP的系统是一种多功能载体,能够负载各种药物分子,最终产生深远的抗增殖作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d693/6768026/11202f0f4804/13065_2018_482_Fig1_HTML.jpg

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