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多柔比星和 4-硝基查耳酮负载于蜂蜡基纳米结构脂质载体:体外抗肿瘤筛选及对 HepG-2 细胞协同作用的评价。

Doxorubicin and 4-nitrochalcone loaded in beeswax-based nanostructured lipid carriers: In vitro antitumoral screening and evaluation of synergistic effect on HepG-2 cells.

机构信息

Department of Chemical and Food Engineering, Federal University of Santa Catarina, SC, Brazil.

Department of Biochemistry, Center for Biological Sciences, Federal University of Santa Catarina, SC, Brazil.

出版信息

Int J Pharm. 2024 Dec 5;666:124788. doi: 10.1016/j.ijpharm.2024.124788. Epub 2024 Oct 3.

Abstract

Cancer is the second most deadly disease worldwide, and the most traditional approaches such as chemotherapy still face limitations associated to drug dosage and off-target side effects. To address these issues, we propose the simultaneous administration of 4-Nitrochalcone (4NC) and Doxorubicin (DOX) using beeswax based nanostructured lipid carriers (NLCs). The co-encapsulation of 4NC and DOX in the beeswax based NLCs was performed using the water/oil/water double emulsion technique in association with the melt dispersion approach. The system composed by semi-spherical NLCs with an average diameter around 200 nm and narrow size distribution, displayed colloidal stability before and after redispersion, keeping the zeta potential below -30 mV. The antitumor activity of the nanoparticles was screened on different tumor cell lines, and the induced cellular death and internal ROS levels were analyzed on hepatocarcinoma cells, which were found to be more affected by the combination of 4NC and DOX. The results indicated that 4NC + DOX-NCLs could promote cytotoxicity and oxidative damage-mediated apoptosis in a HepG-2 cell line.

摘要

癌症是全球第二大致命疾病,而最传统的方法,如化疗,仍然面临着与药物剂量和脱靶副作用相关的限制。为了解决这些问题,我们提出使用蜂蜡基纳米结构化脂质载体(NLC)同时给予 4-硝基查耳酮(4NC)和多柔比星(DOX)。采用水/油/水双乳液技术结合熔融分散法,将 4NC 和 DOX 共同包封在蜂蜡基 NLC 中。由平均直径约 200nm 的半球形 NLC 组成的系统具有窄的粒径分布,在重新分散前后表现出胶体稳定性,其 Zeta 电位保持在-30mV 以下。在不同的肿瘤细胞系上筛选了纳米粒子的抗肿瘤活性,并在肝癌细胞上分析了诱导的细胞死亡和内部 ROS 水平,发现 4NC 和 DOX 的联合对肝癌细胞的影响更大。结果表明,4NC+DOX-NCLs 可促进 HepG-2 细胞系的细胞毒性和氧化损伤介导的细胞凋亡。

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