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负载姜黄素的纳米结构混合脂质胶囊用于协同根除乳腺癌和癌症干细胞并增强抗癌疗效

Curcumin-Loaded Nanostructure Hybrid Lipid Capsules for Co-eradication of Breast Cancer and Cancer Stem Cells with Enhanced Anticancer Efficacy.

作者信息

Yadava Sunil Kumar, Basu Suparna Mercy, Valsalakumari Remya, Chauhan Meenakshi, Singhania Mekhla, Giri Jyotsnendu

机构信息

Department of Biomedical Engineering, Indian Institute of Technology (IIT Hyderabad), Hyderabad 502285, India.

Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, Minnesota 55455, United States.

出版信息

ACS Appl Bio Mater. 2020 Oct 19;3(10):6811-6822. doi: 10.1021/acsabm.0c00764. Epub 2020 Oct 8.

Abstract

Co-eradication of cancer stem cells (CSCs) along with cancer cells have emerged as an immediate necessity to combat the rapid progression, therapeutic resistance, and relapse of cancer. Curcumin (CMN) has been well established for anticancer activity against a variety of cancers with an ability to eliminate CSCs. In spite of its extensive therapeutic potential, clinical applicability is impeded due to its highly hydrophobic nature. In this study, we developed CMN-loaded nanostructure hybrid lipid capsules (CMN-nHLCs) of three sizes (25, 75, and 150 nm) with 4% (w/w) loading capacity using our low-temperature (LT) method. Molecular interaction between different ingredients using fourier transform infrared (FTIR) analysis shows self-arrangement of ingredients into CMN-loaded nHLCs without any chemical bonding. CMN-nHLCs show a controlled release of CMN from nHLCs at 37 °C and long-term storage stability at 4 °C. CMN-nHLCs show ∼2.5-fold enhanced anticancer efficacy compared to free CMN in breast cancer cells (non-bCSCs) and breast cancer stem-like cells (bCSCs). CMN-nHLCs are effectively internalized into MCF-7 cells (non-bCSCs and bCSCs) and cause significant reduction in their mammosphere size/number and stemness. nHLCs provide improved physicochemical properties of CMN and superior anticancer efficacy by co-eradiating both non-bCSCs and bCSCs, suggesting a promising candidature of CMN-nHLCs for breast cancer treatment.

摘要

与癌细胞共同根除癌症干细胞(CSCs)已成为对抗癌症快速进展、治疗抗性和复发的当务之急。姜黄素(CMN)对多种癌症具有抗癌活性并能够消除癌症干细胞,这一点已得到充分证实。尽管其具有广泛的治疗潜力,但由于其高度疏水的性质,其临床适用性受到阻碍。在本研究中,我们使用低温(LT)方法制备了三种尺寸(25、75和150纳米)、载药量为4%(w/w)的负载CMN的纳米结构混合脂质胶囊(CMN-nHLCs)。利用傅里叶变换红外(FTIR)分析不同成分之间的分子相互作用,结果表明各成分自行排列形成负载CMN的nHLCs,且不存在任何化学键。CMN-nHLCs在37℃时能从nHLCs中实现CMN的控释,并在4℃下具有长期储存稳定性。与游离CMN相比,CMN-nHLCs在乳腺癌细胞(非bCSCs)和乳腺癌干细胞样细胞(bCSCs)中显示出约2.5倍增强的抗癌功效。CMN-nHLCs能有效内化进入MCF-7细胞(非bCSCs和bCSCs),并使其乳腺球大小/数量和干性显著降低。nHLCs改善了CMN的物理化学性质,并通过共同根除非bCSCs和bCSCs而具有卓越的抗癌功效,这表明CMN-nHLCs在乳腺癌治疗方面具有广阔前景。

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