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姜黄素负载的脂质体@海藻酸钙纳米载体的制备、优化及体外评价:一种乳腺癌治疗的新方法

Preparation, Optimization and In-Vitro Evaluation of Curcumin-Loaded Niosome@calcium Alginate Nanocarrier as a New Approach for Breast Cancer Treatment.

作者信息

Akbarzadeh Iman, Shayan Mona, Bourbour Mahsa, Moghtaderi Maryam, Noorbazargan Hassan, Eshrati Yeganeh Faten, Saffar Samaneh, Tahriri Mohammadreza

机构信息

Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran 145888-9694, Iran.

Core Facility Center, Pasteur Institute of Iran, Tehran 1316943551, Iran.

出版信息

Biology (Basel). 2021 Feb 26;10(3):173. doi: 10.3390/biology10030173.

Abstract

Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box-Behnken design-in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that-thanks to its biocompatibility toward normal cells-the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.

摘要

癌症是最常见的死亡原因之一,其各种治疗方法可能给患者带来诸多挑战。作为应用最广泛的癌症治疗方法之一,化疗可能会导致多种副作用。缺乏靶向肿瘤组织的药物递送会增加对健康组织造成损伤的可能性,并伴随功能障碍。在本研究中,通过三级Box-Behnken设计,在尺寸和载药效率方面开发并优化了一种具有海藻酸钙壳的载姜黄素脂质体(AL-NioC)的最佳配方。通过透射电子显微镜、傅里叶变换红外光谱和动态光散射对脂质体进行了表征。所制备的脂质体在4℃下显示出长达1个月的优异稳定性。此外,脂质体制剂表现出pH依赖性释放;在生理pH(7.4)下呈缓释曲线,在酸性条件(pH = 3)下释放速率更高。细胞毒性研究表明,AL-NioC对正常MCF10A细胞具有高度相容性,而在MDA-MB-231和SKBR3乳腺癌细胞中观察到显著毒性。癌细胞的基因表达研究表明,经过设计的治疗后,Bcl2、细胞周期蛋白D和细胞周期蛋白E基因下调,同时P53、Bax、半胱天冬酶-3和半胱天冬酶-9基因表达上调。流式细胞术研究证实,与其他样品相比,在MDA-MB-231和SKBR3细胞中存在AL-NioC时,凋亡率显著提高。总体而言,本研究结果表明,由于AL-NioC对正常细胞具有生物相容性,该配方可以有效地将疏水性药物递送至靶向癌细胞,同时减少副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d84/7996962/7413f6c522ca/biology-10-00173-g001.jpg

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