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多巴胺与牛血清白蛋白及沸石咪唑骨架共轭物的工程化:一种有前景的肺癌细胞药物递送纳米载体

Engineering of dopamine conjugated with bovine serum albumin and zeolite imidazole framework: A promising drug delivery nanocarrier on lung cancer cells.

作者信息

Lei Chenggang, Liu Di, Zhou Qian, Ma Shengwei, Qian Haiyun

机构信息

Department of Cardiothoracic Surgery, Jingzhou Hospital Affiliated to Yangtze University, No.26, Chuyuan Road, Jingzhou District, Jingzhou City, Hubei Province, 434020, China.

出版信息

Heliyon. 2024 Aug 20;10(17):e36580. doi: 10.1016/j.heliyon.2024.e36580. eCollection 2024 Sep 15.

Abstract

Modern, highly abundant materials called metal-organic structures (MOF) comprise metal ions and organic coordinating molecules and have attracted attention as potential biomedical materials due to their unusual properties. In the present study, the anticancer drug sorafenib (SF) and the Kaempferol (KM) were encapsulated in a nanocomposite made of bovine serum albumin (BA) as the core and pH-dependent zeolitic imidazolate framework-8 (ZIF) coating. To develop a multifunctional nanocarrier, polydopamine, Au chelation, and gallic acid (GL) conjugation were used to build BA@SF@ZIF and BA@SF@ZIF/KM. A variety of characterisation techniques verified the success of the nanocarrier's fabrication. Studies in vitro exhibited that BA@SF@ZIF/DA/GL and BA@SF@ZIF/KM/DA/GL released their respective ligands in a pH-dependent manner due to ZIF-8. These nanocarriers' cytotoxicity and apoptotic effects were measured with the MTT evaluation. Morphological and nuclear damage staining in A549 and H1299 human lung cancer cells. The cytotoxicity investigation displayed that BA@SF@ZIF/DA/GL and BA@SF@ZIF/KM/DA/GL were more efficient than free sorafenib in A549 and H1299 cells with less toxicity in HUVECs. The DNA fragmentation of the cells was assessed by utilizing the comet assay. BA@SF@ZIF/KM/DA/GL increased ROS levels and caused mitochondrial membrane potential and DNA damage, which resulted in apoptosis. Therefore, we believe the developed smart BA@SF@ZIF/KM/DA/GL could be a promising therapeutic approach using sorafenib for lung cancer therapy.

摘要

现代的、含量丰富的金属有机结构(MOF)由金属离子和有机配位分子组成,因其独特性质而作为潜在生物医学材料受到关注。在本研究中,抗癌药物索拉非尼(SF)和山奈酚(KM)被包裹在以牛血清白蛋白(BA)为核心、pH依赖型沸石咪唑酯骨架-8(ZIF)为涂层的纳米复合材料中。为开发多功能纳米载体,利用聚多巴胺、金螯合和没食子酸(GL)共轭构建了BA@SF@ZIF和BA@SF@ZIF/KM。多种表征技术证实了纳米载体制造成功。体外研究表明,由于ZIF-8,BA@SF@ZIF/DA/GL和BA@SF@ZIF/KM/DA/GL以pH依赖方式释放各自的配体。通过MTT评估测定了这些纳米载体的细胞毒性和凋亡作用。对A549和H1299人肺癌细胞进行形态学和核损伤染色。细胞毒性研究显示,BA@SF@ZIF/DA/GL和BA@SF@ZIF/KM/DA/GL在A549和H1299细胞中比游离索拉非尼更有效,对人脐静脉内皮细胞(HUVECs)毒性更小。利用彗星试验评估细胞的DNA片段化。BA@SF@ZIF/KM/DA/GL增加活性氧(ROS)水平,导致线粒体膜电位和DNA损伤,从而引发凋亡。因此,我们认为所开发的智能BA@SF@ZIF/KM/DA/GL可能是一种使用索拉非尼治疗肺癌的有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c51/11401118/73c2810dd167/gr1.jpg

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