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新型纳米脂质体通过阿霉素卓越的细胞内摄取增强了对MCF-7乳腺癌细胞的抑制作用。

Novel -derived nanoliposomes enhance the inhibition of MCF-7 breast cancer cells by superb intracellular uptake of doxorubicin.

作者信息

Asadi Zahra, Arkan Elham, Nowroozi Ghazal, Aghaz Faranak

机构信息

Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Heliyon. 2024 Sep 26;10(19):e38337. doi: 10.1016/j.heliyon.2024.e38337. eCollection 2024 Oct 15.

Abstract

In this study, we aimed to utilize phospholipids from the bacterium Pseudomonas putida (PP) as a plentiful, safe, and accessible resource for creating nanoliposomes to deliver doxorubicin (Dox) to MCF-7 breast cancer cells. This bacterium provides a cost-effective source of phospholipids commonly used in nanoliposome production, with no toxicity or adverse environmental impact. To this end, molecular dynamics (MD) simulations were first conducted to evaluate the feasibility of this approach and to analyze the behavior and interaction of Dox with the nanoliposomes. The phospholipids of PP were then extracted using Folch's technique. Subsequently, Dox-loaded PP-derived nanoliposomes (PNL-Dox) were developed using the thin-film method. The physicochemical properties of the fabricated nanocarrier were then investigated and the anticancer effects of this system were tested on MCF-7 cells. The results of the MD simulations indicated that Dox reacted with all of the phospholipids through hydrogen bonds without affecting the fluidity, stability, and thickness of the nanoliposome membrane. Additionally, a small number of Dox molecules interacted with the nanocarrier membrane, while the remaining were located in its interior. The physicochemical investigation results showed that PNL-Dox had an average particle size and zeta potential of 271.7 ± 7.1 nm and -8.8 ± 3.3 mV, respectively. Scanning electron microscopy revealed that the particles were spherical and did not show any signs of aggregation. Drug release of PNL-Dox was gradual at pH 7.4 and 6.5, with a significantly higher release at pH 6.5. In vitro studies demonstrated successful uptake of PNL-Dox by MCF-7 cells, resulting in cytotoxicity within 24 and 48 h of treatment. Also, it increased apoptosis and reduced the production of reactive oxygen species (ROS) in these cells. Our study showcased the potential of PP phospholipids to form a promising anti-cancer drug delivery system, opening up new possibilities for the treatment of all types of cancers.

摘要

在本研究中,我们旨在利用恶臭假单胞菌(PP)中的磷脂作为一种丰富、安全且易于获取的资源,用于制备纳米脂质体,以将阿霉素(Dox)递送至MCF-7乳腺癌细胞。这种细菌提供了一种常用于纳米脂质体生产的具有成本效益的磷脂来源,且无毒且对环境无不良影响。为此,首先进行了分子动力学(MD)模拟,以评估该方法的可行性,并分析Dox与纳米脂质体的行为及相互作用。然后采用福氏提取法提取PP的磷脂。随后,使用薄膜法制备了载有Dox的PP衍生纳米脂质体(PNL-Dox)。接着研究了所制备纳米载体的物理化学性质,并在MCF-7细胞上测试了该系统的抗癌效果。MD模拟结果表明,Dox通过氢键与所有磷脂发生反应,而不影响纳米脂质体膜的流动性、稳定性和厚度。此外,少量Dox分子与纳米载体膜相互作用,其余的则位于其内部。物理化学研究结果表明,PNL-Dox的平均粒径和zeta电位分别为271.7±7.1 nm和-8.8±3.3 mV。扫描电子显微镜显示颗粒呈球形,未显示任何聚集迹象。PNL-Dox在pH 7.4和6.5时药物释放缓慢,在pH 6.5时释放显著更高。体外研究表明MCF-7细胞成功摄取了PNL-Dox,在处理24和48小时内产生了细胞毒性。此外,它还增加了这些细胞的凋亡并减少了活性氧(ROS)的产生。我们的研究展示了PP磷脂形成有前景的抗癌药物递送系统的潜力,为治疗所有类型的癌症开辟了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f930/11471583/c42e80020ce8/ga1.jpg

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