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载有姜黄素的亲和体修饰脂质体对乳腺癌细胞系的细胞毒性评估

Cytotoxicity evaluation of curcumin-loaded affibody-decorated liposomes against breast cancerous cell lines.

作者信息

Moballegh-Nasery Mahshid, Mandegary Ali, Eslaminejad Touba, Zeinali Majid, Pardakhti Abbas, Behnam Behzad, Mohammadi Mohadeseh

机构信息

Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

J Liposome Res. 2021 Jun;31(2):189-194. doi: 10.1080/08982104.2020.1755981. Epub 2020 Jul 3.

Abstract

Curcumin is known as an effective anticancer herbal medicine but unfortunately, its bioavailability is poor which necessitate efforts for developing more efficient and specific delivery systems. Human epidermal growth factor receptor 2 (HER 2) due to its overexpression in various types of cancers, is demonstrated to be a good candidate as a target for anticancer therapy. In this study, cytotoxicity of curcumin encapsulated in ZHER2:342 Affibody-decorated liposome was investigated against SKBR3 and MCF-7 cancerous cell lines. Curcumin-containing liposomes were prepared from soybeans lecetin and cholesterol by thin-film hydration method. Affibody ZHER2:342 molecules C-terminal cysteine residue were conjugated covalently to the prepared liposomes. Particle size analysis was performed using atomic force microscopy (AFM) and dynamic light scattering (DLS). Curcumin loading was measured using UV-Vis spectrophotometry and cytotoxic activity of curcumin formulations against cancerous cell lines was investigated by MTT assay. Induction of apoptosis was investigated using flow cytometry through Annexin V staining. Particle analysis showed the formation of spherical liposomes with a mean diameter of about 150 nm. Cytotoxic activity of curcumin was improved by its encapsulation in both liposomes and affibody-decorated liposomes. The Annexin V staining indicated the induction of apoptosis by affibody-decorated liposomes in both MCF-7 and SKBR3 cells. Decoration of curcumin-loaded liposomes with affibody ZHER2:342 may improve curcumin apoptotic function independently of HER2 expression level.

摘要

姜黄素是一种有效的抗癌草药,但不幸的是,其生物利用度较差,因此需要努力开发更高效、更具特异性的递送系统。人表皮生长因子受体2(HER 2)由于在各种癌症中过度表达,被证明是抗癌治疗的一个良好靶点。在本研究中,研究了包封在ZHER2:342亲和体修饰脂质体中的姜黄素对SKBR3和MCF-7癌细胞系的细胞毒性。含姜黄素的脂质体由大豆卵磷脂和胆固醇通过薄膜水化法制备。将亲和体ZHER2:342分子的C末端半胱氨酸残基共价偶联到制备的脂质体上。使用原子力显微镜(AFM)和动态光散射(DLS)进行粒度分析。使用紫外可见分光光度法测量姜黄素负载量,并通过MTT法研究姜黄素制剂对癌细胞系的细胞毒性活性。通过膜联蛋白V染色,使用流式细胞术研究细胞凋亡的诱导情况。粒度分析表明形成了平均直径约为150nm的球形脂质体。姜黄素包封在脂质体和亲和体修饰脂质体中均提高了其细胞毒性活性。膜联蛋白V染色表明亲和体修饰脂质体在MCF-7和SKBR3细胞中均诱导了细胞凋亡。用亲和体ZHER2:342修饰负载姜黄素的脂质体可能会改善姜黄素的凋亡功能,而与HER2表达水平无关。

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