用于提高乳腺癌治疗用来曲唑的递送和抗癌活性的控释纳米囊泡的体外研究
In vitro Development of Controlled-Release Nanoniosomes for Improved Delivery and Anticancer Activity of Letrozole for Breast Cancer Treatment.
机构信息
Department of Nano Biotechnology, New Technology Research Group, Pasteur Institute of Iran, Tehran, Iran.
Integrative Research Laboratory, Islamic Azad University of Medical Sciences, Tehran, Iran.
出版信息
Int J Nanomedicine. 2022 Dec 11;17:6233-6255. doi: 10.2147/IJN.S384085. eCollection 2022.
INTRODUCTION
Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast cancer cell lines.
MATERIALS AND METHODS
Various niosomal formulations of letrozole were fabricated through thin-film hydration method and characterized in terms of size, polydispersity index (PDI), morphology, entrapment efficiency (EE%), release kinetics, and stability. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). Antiproliferative activity and the mechanism were assessed by MTT assay, quantitative real-time PCR, and flow cytometry. Furthermore, cellular uptake of optimum formulation was evaluated by confocal electron microscopy.
RESULTS
The formulated letrozole had a spherical shape and showed a slow-release profile of the drug after 72 h. The size, PDI, and eEE% of nanoparticles showed higher stability at 4°C compared with 25°C. The drug release from niosomes was in accordance with Korsmeyer-Peppa's kinetic model. Confocal microscopy revealed the localization of drug-loaded niosomes in the cancer cells. MTT assay revealed that all samples exhibited dose-dependent cytotoxicity against breast cancer cells. The IC of mixed formulation of letrozole with letrozole-loaded niosome (L + L) is the lowest value among all prepared formulations. L+L influenced the gene expression in the tested breast cancer cell lines by down-regulating the expression of gene while up-regulating the expression of and genes. The flow cytometry results revealed that L + L enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L), and control sample.
CONCLUSION
Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.
简介
乳腺癌是全球女性中最常见的致命癌症之一。在本研究中，我们开发了一种来曲唑的最佳配方，即载来曲唑的脂质体和空白脂质体，并在体外 MCF-7、MCF10A 和 MDA-MB-231 乳腺癌细胞系中评估了其抗癌效果。
材料和方法
通过薄膜水化法制备了各种来曲唑的脂质体配方，并根据粒径、多分散指数（PDI）、形态、包封效率（EE%）、释放动力学和稳定性进行了表征。通过响应面法（RSM）优化了来曲唑的脂质体配方。通过 MTT 测定法、实时定量 PCR 和流式细胞术评估了增殖抑制活性和作用机制。此外，通过共聚焦电子显微镜评估了最佳配方的细胞摄取。
结果
所制备的来曲唑呈球形，在 72 小时后显示出药物的缓慢释放特征。与 25°C 相比，纳米粒的粒径、PDI 和 eEE%在 4°C 下显示出更高的稳定性。药物从脂质体中的释放符合 Korsmeyer-Peppa 动力学模型。共聚焦显微镜显示载药脂质体在癌细胞中的定位。MTT 测定法表明，所有样品对乳腺癌细胞均表现出剂量依赖性细胞毒性。混合制剂（载来曲唑的脂质体与来曲唑的混合物，L + L）的 IC 是所有制备制剂中最低的。L + L 通过下调 基因的表达，同时上调 基因和 基因的表达，影响了测试乳腺癌细胞系中的基因表达。流式细胞术结果表明，与来曲唑（L）、载来曲唑的脂质体（L）和对照样品相比，L + L 增加了 MCF-7 和 MDA-MB-231 细胞系中的凋亡率。
结论
结果表明，脂质体可以作为来曲唑递送到乳腺癌细胞的有前途的药物载体。
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