a Department of Biology, Faculty of Natural Sciences , University of Tabriz , Tabriz , Iran.
b Department of Medical Biotechnology, Faculty of Advanced Medical Sciences , Tabriz University of Medical Sciences , Tabriz , Iran.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):737-746. doi: 10.1080/21691401.2019.1573737.
Metformin (MET) has received considerable attention in recent years for its anticancer potential activities. However, short half-life and weak bioavailability of MET limited its use as a chemotherapeutic agent. The present study is intended to evaluate the efficiency of PLGA-PEG as a nano-carrier for MET to increase anticancer effects on SKOV3 ovarian carcinoma cells. MET-loaded PLGA-PEG nanoparticles (NPs) were characterized through Dynamic Light Scattering (DLS), Fourier-transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FE-SEM). Anti-proliferative and apoptotic effects of nanoformulated MET were evaluated using MTT and flow-cytometric assays, respectively. Also, real-time polymerase chain reaction (Real-Time PCR) was used to determine the gene expression levels of apoptotic genes, p53 and hTERT. Evaluation of cytotoxicity showed that MET-NPs had more cytotoxicity than free MET in a time-and dose-dependent manner. The nuclei fragmentation and the percentage of apoptotic cells induced by MET-NPs were significantly higher than free MET. Also, it was found that MET-NPs triggered more cell cycle arrest at sub-G1 checkpoint than free MET. Compared to MET treated cells, the mRNA expression levels of apoptotic genes, as well as p53 and hTERT were significantly altered in MET-NPs treated cells. In conclusion, it is supposed that nano-encapsulation of MET into polymeric PLGA-PEG NPs may be a convenient drug delivery system to enhance its anticancer effects for ovarian cancer therapy.
近年来，二甲双胍（MET）因其潜在的抗癌活性而受到广泛关注。然而，MET 的半衰期短和生物利用度低限制了其作为化疗药物的应用。本研究旨在评估 PLGA-PEG 作为 MET 的纳米载体以提高其对 SKOV3 卵巢癌细胞的抗癌作用的效率。通过动态光散射（DLS）、傅里叶变换红外光谱（FTIR）和场发射扫描电子显微镜（FE-SEM）对载有 MET 的 PLGA-PEG 纳米粒子（NPs）进行了表征。使用 MTT 和流式细胞术分别评估了纳米制剂 MET 的抗增殖和促凋亡作用。此外，还使用实时聚合酶链反应（Real-Time PCR）来确定凋亡基因、p53 和 hTERT 的基因表达水平。细胞毒性评估表明，MET-NPs 比游离 MET 具有更高的细胞毒性，且呈时间和剂量依赖性。与游离 MET 相比，MET-NPs 诱导的核碎片和凋亡细胞的百分比明显更高。此外，与游离 MET 相比，MET-NPs 更能引发细胞周期在 sub-G1 检查点的阻滞。与 MET 处理的细胞相比，MET-NPs 处理的细胞中凋亡基因以及 p53 和 hTERT 的 mRNA 表达水平明显改变。总之，将 MET 纳米封装到聚合物 PLGA-PEG NPs 中可能是一种增强其对卵巢癌治疗的抗癌作用的方便的药物传递系统。
