a Department of Molecular Biology and Genetics, Faculty of Arts and Science , Istanbul Bilim University , Istanbul , Turkey.
b Department of Molecular Biology and Genetics, Faculty of Arts and Science , Yildiz Technical University , Istanbul , Turkey.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):319-329. doi: 10.1080/21691401.2018.1556213.
The aim of this study was to evaluate anti-cancer properties of hesperetin (Hsp) and hesperetin-loaded poly(lactic-co-glycolic acid) nanoparticles (HspNPs) for glioblastoma treatment. Nanoparticles prepared by single emulsion method had a size of less than 300 nm with 70.7 ± 3.9% reaction yield and 26.4 ± 1.1% Hsp loading capacity. Treatment of C6 glioma cells with HspNPs for 24 and 48 h resulted in dose- and time-dependent decrease in cell viability, with approximate IC of 28 and 21 μg/mL, respectively (p = .036 for 24 h, p = .025 for 48 h). The percentage of PCNA positive cells decreased to 20% and 10%, respectively, for Hsp- and HspNP-treated cells at concentration of 100 µg/mL. Treatment with increasing concentrations of HspNPs (25, 50, 75 and 100 µg/mL) resulted in 9.1-, 7-, 12.5- and 12.7-fold in increase in apoptotic cell number. Optimum doses of Hsp and HspNPs were found to increase oxidative damage in C6 glioma cells. MDA levels, an indicator of lipid peroxidation, were found to be significantly elevated at 75 and 100 µg/mL exposure concentration of HspNPs with (p = .002) and (p = .018), respectively for 48-h treatment. The results obtained with this study showed biocompatible polymeric nanoparticle systems has great advantages to enhance anti-cancer activity and poor solubility of therapeutic agents. Overall our findings suggest that Hsp-loaded PLGA nanoparticle systems showed significant anti-cancer activity and HspNPs could be used as promising novel anti-cancer agent.
本研究旨在评估橙皮苷（Hsp）及其负载于聚乳酸-羟基乙酸共聚物纳米粒（HspNPs）的抗癌特性，用于治疗神经胶质瘤。通过单乳液法制备的纳米粒粒径小于 300nm，反应产率为 70.7±3.9%，Hsp 载药量为 26.4±1.1%。HspNPs 处理 C6 神经胶质瘤细胞 24 和 48h 后，细胞活力呈剂量和时间依赖性下降，其近似 IC 分别为 28 和 21μg/mL（p=0.036 于 24h，p=0.025 于 48h）。Hsp 和 HspNP 处理浓度为 100μg/mL 时，PCNA 阳性细胞的百分比分别降至 20%和 10%。用浓度逐渐增加的 HspNPs（25、50、75 和 100μg/mL）处理细胞，可使凋亡细胞数分别增加 9.1、7、12.5 和 12.7 倍。Hsp 和 HspNPs 的最佳剂量被发现可增加 C6 神经胶质瘤细胞的氧化损伤。丙二醛（MDA）水平作为脂质过氧化的标志物，在 HspNPs 暴露浓度为 75 和 100μg/mL 时，分别显著升高（p=0.002 和 p=0.018），分别用于 48h 处理。本研究结果表明，生物相容性聚合物纳米粒系统具有增强抗癌活性和改善治疗剂溶解度的巨大优势。总的来说，我们的研究结果表明，负载 Hsp 的 PLGA 纳米粒系统表现出显著的抗癌活性，HspNPs 可作为有前途的新型抗癌药物。
