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用叶酸功能化的包裹他莫昔芬的荧光纳米胶囊,用于增强对乳腺癌细胞系MCF-7的药物递送和癌细胞成像。

Fluorescent tamoxifen-encapsulated nanocapsules functionalized with folic acid for enhanced drug delivery toward breast cancer cell line MCF-7 and cancer cell imaging.

作者信息

Nankali Ehsan, Shaabanzadeh Masoud, Torbati Maryam Bikhof

机构信息

Department of Chemistry, Damghan Branch, Islamic Azad University, Damghan, Iran.

Department of Biology, Yadegar-e-Imam Khomeini (RAH) Shahr-e-Rey Branch, Islamic Azad University, Tehran, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2020 Jul;393(7):1211-1219. doi: 10.1007/s00210-020-01825-1. Epub 2020 Jan 24.

Abstract

Nanoscale drug delivery systems such as nanocapsules at the convergence of nanotechnology and biomedical sciences have been widely used. In the present study, with the aim of simultaneous imaging and therapy of cancer cells based on biodegradable/biocompatible polymers, we designed and synthesized tamoxifen-encapsulated nanocapsules to target the folate receptor positive breast cancer cells. Noteworthy, to monitor and link to the cancer cells, these nanocapsules were functionalized with fluorescein isothiocyanate and folic acid. The synthesized nanocapsules were characterized by FTIR, XRD, and PL spectroscopy, as well as FESEM and TEM techniques. Although the free tamoxifen has low solubility in physiological solutions, the synthesized tamoxifen-encapsulated nanocapsules have enough solubility, good stability, and more biocompatibility in these solutions. The encapsulation of tamoxifen into the nanocapsules, tamoxifen loading, and its subsequent release behavior were studied. In order to investigate the biological role of these nanocapsules, MTT assay and cell imaging analysis have also been examined. The cytotoxicity test exhibit that the mean IC values on the MCF-7 cell line were found to be 15.52 and 8.46 μg/ml in 24 h and 48 h respectively and the cytotoxicity increased by approximately 2.72-fold compared with free TAM against the MCF-7 cancer cell line. Also, cell imaging experiments showed that the synthesized nanocapsules have appropriate cellular uptake efficiency, good potential for monitoring of these particles in vitro. The experimental results suggest that the synthesized tamoxifen nanocapsules facilitate the proper targeting, drug encapsulation efficiency, and controlled release of tamoxifen in vitro.

摘要

纳米技术与生物医学科学交叉领域的纳米级药物递送系统,如纳米胶囊,已被广泛应用。在本研究中,为了基于可生物降解/生物相容性聚合物对癌细胞进行同步成像和治疗,我们设计并合成了包载他莫昔芬的纳米胶囊,以靶向叶酸受体阳性的乳腺癌细胞。值得注意的是,为了监测并与癌细胞建立联系,这些纳米胶囊用异硫氰酸荧光素和叶酸进行了功能化修饰。通过傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)、光致发光光谱(PL)以及场发射扫描电子显微镜(FESEM)和透射电子显微镜(TEM)技术对合成的纳米胶囊进行了表征。尽管游离他莫昔芬在生理溶液中的溶解度较低,但合成的包载他莫昔芬的纳米胶囊在这些溶液中具有足够的溶解度、良好的稳定性和更高的生物相容性。研究了他莫昔芬在纳米胶囊中的包封、载药量及其随后的释放行为。为了研究这些纳米胶囊的生物学作用,还进行了MTT法检测和细胞成像分析。细胞毒性试验表明,在24小时和48小时时,MCF - 7细胞系上的平均半数抑制浓度(IC)值分别为15.52和8.46μg/ml,与游离他莫昔芬相比,对MCF - 7癌细胞系的细胞毒性增加了约2.72倍。此外,细胞成像实验表明,合成的纳米胶囊具有适当的细胞摄取效率,在体外监测这些颗粒具有良好的潜力。实验结果表明,合成的他莫昔芬纳米胶囊在体外促进了他莫昔芬的靶向性、药物包封效率和控释。

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