Askar Mostafa A, El-Nashar Heba As, Al-Azzawi Mahmood A, Rahman Sahar S Abdel, Elshawi Omama E
Department of Radiation Biology, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt.
Department of Pharmacognosy and Center of Drug Discovery Research and Development, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Breast Cancer (Auckl). 2022 Mar 25;16:11782234221086728. doi: 10.1177/11782234221086728. eCollection 2022.
Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus . Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.
槲皮素是一种存在于水果和蔬菜中的强效癌症治疗剂。由于存在许多与低溶解度、生物利用度、渗透性和不稳定性相关的问题，槲皮素的药用受到限制。此外，高剂量的槲皮素在临床和实验研究中显示出毒性作用。因此，需要一种新的策略来克服这些问题，且不使用有毒剂量。氧化铁纳米颗粒可用作药物递送系统。本研究旨在利用生物简单纳米沉淀法并在真菌介导下制备槲皮素共轭磁铁矿纳米颗粒（QMNPs）。此外，我们开展了体外和体内研究，以确定QMNPs是否能使乳腺癌对放射治疗敏感。对制备的纳米颗粒的结构、形态和磁性进行了研究。结果表明，QMNPs呈球形，直径为40纳米。体外研究表明，将MCF-7、HePG-2和A459癌细胞与QMNPs孵育24小时，能以浓度依赖的方式有效抑制癌细胞系的生长，IC50值分别为11、77.5和104纳摩尔/毫升。QMNPs与辐射（IR）联合使用能有效阻断MCF-7癌细胞的增殖，并且通过明场倒置光学显微镜观察发现这些细胞的形态有显著变化。针对QMNPs（20毫升/千克）的长期毒性进行评估，血液学、肝脏和肾脏标志物的检测结果表明没有毒性作用。此外，QMNPs抑制了雌性白化病大鼠中由N-甲基-N-亚硝基脲（MNU）诱导的乳腺癌的肿瘤生长，并显著增强了侧向放射治疗效果。这些抗癌和放射增敏活性归因于细胞毒性、细胞周期阻滞、免疫调节以及通过诱导凋亡产生的效果。总之，这些观察结果表明，QMNPs与低剂量放疗联合使用可作为乳腺癌的一种潜在靶向治疗方法。
