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包覆细菌多糖的硒纳米颗粒作为抗肺癌药物的体外和体内研究

In vitro and in vivo studies of selenium nanoparticles coated bacterial polysaccharide as anti-lung cancer agents.

作者信息

Shehata Nourhan S, Elwakil Bassma H, Elshewemi Salma S, Ghareeb Doaa A, Olama Zakia A

机构信息

Department of Medical Laboratory Technology, Faculty of Applied Health Sciences Technology, Pharos University in Alexandria, Alexandria, Egypt.

Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt.

出版信息

Microb Cell Fact. 2024 Dec 19;23(1):339. doi: 10.1186/s12934-024-02601-z.

Abstract

Microbial exopolysaccharides (EPSs) possess valuable biological functions and fascinating physicochemical properties. On the other hand, lung cancer is the primary contributor to global cancer-related deaths. However, health and safety concerns have prevented the identification and approval of any medications, including chemotherapeutic agents, for lung cancer treatment to date. The current study aims to enhance the production of bacterial EPS as a coating agent for the synthesis of selenium nanoparticles (AZEPS-SeNPs), to enhance their biological activity against pathogenic microbes, human lung adenocarcinoma cells (A549) in vitro, and diethyl nitrosamine (DEN)-induced lung cancer in vivo. The synthesized AZEPS-SeNPs exhibited a significant antifungal effect reaching 49.3 mm against Candida albicans. SeNPs and EPSs demonstrated a concentration-dependent synergistic antioxidant effect of 96.8%. Moreover, the synthesized nanoparticles showed a highly potent cytotoxic effect against A549 cells (1.724 ± 0.08 µg/mL) with a therapeutic index of 7.18 ± 0.21 that leads to increased reactive oxygen species (ROS) production. AZEPS-SeNPs demonstrated a proapoptotic effect on the lung adenocarcinoma A549 cell line by stimulating caspase 3 and Bax (7.08-fold and 6.505-fold, respectively), inhibiting the anti-apoptotic gene Bcl2, and arresting the cell cycle in the S phase. In vivo study revealed that the AZEPS-SeNPs-treated group showed improved histopathological examination of lung tissue sections. The present study concluded the efficiency of the synthesized bacterial EPS-SeNPs as multi-functional antimicrobial, anticancer and antioxidant agent.

摘要

微生物胞外多糖(EPSs)具有重要的生物学功能和迷人的物理化学性质。另一方面,肺癌是全球癌症相关死亡的主要原因。然而,健康和安全问题阻碍了包括化疗药物在内的任何肺癌治疗药物的鉴定和批准。目前的研究旨在提高细菌EPS作为合成硒纳米颗粒(AZEPS-SeNPs)的包衣剂的产量,以增强其对致病微生物、体外人肺腺癌细胞(A549)以及体内二乙基亚硝胺(DEN)诱导的肺癌的生物活性。合成的AZEPS-SeNPs对白色念珠菌表现出显著的抗真菌作用,抑菌圈直径达49.3毫米。SeNPs和EPSs表现出浓度依赖性的协同抗氧化作用,协同率为96.8%。此外,合成的纳米颗粒对A549细胞显示出高效的细胞毒性作用(1.724±0.08微克/毫升),治疗指数为7.18±0.21,导致活性氧(ROS)生成增加。AZEPS-SeNPs通过刺激半胱天冬酶3和Bax(分别为7.08倍和6.505倍)、抑制抗凋亡基因Bcl2以及使细胞周期停滞在S期,对肺腺癌A549细胞系表现出促凋亡作用。体内研究表明,AZEPS-SeNPs治疗组的肺组织切片组织病理学检查结果有所改善。本研究得出结论,合成的细菌EPS-SeNPs作为多功能抗菌、抗癌和抗氧化剂具有有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b80c/11658177/5136821e2f9c/12934_2024_2601_Fig1_HTML.jpg

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