Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
National Institute of Materials Physics, 076900 Magurele, Romania.
Int J Mol Sci. 2023 Feb 7;24(4):3307. doi: 10.3390/ijms24043307.
Iron oxide nanoparticles are one of the most promising tools for theranostic applications of pancreatic cancer due to their unique physicochemical and magnetic properties making them suitable for both diagnosis and therapy. Thus, our study aimed to characterize the properties of dextran-coated iron oxide nanoparticles (DIO-NPs) of maghemite (γ-FeO) type synthesized by co-precipitation and to investigate their effects (low-dose versus high-dose) on pancreatic cancer cells focusing on NP cellular uptake, MR contrast, and toxicological profile. This paper also addressed the modulation of heat shock proteins (HSPs) and p53 protein expression as well as the potential of DIO-NPs for theranostic purposes. DIO-NPs were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering analyses (DLS), and zeta potential. Pancreatic cancer cells (PANC-1 cell line) were exposed to different doses of dextran-coated ɣ-FeO NPs (14, 28, 42, 56 μg/mL) for up to 72 h. The results revealed that DIO-NPs with a hydrodynamic diameter of 16.3 nm produce a significant negative contrast using a 7 T MRI scanner correlated with dose-dependent cellular iron uptake and toxicity levels. We showed that DIO-NPs are biocompatible up to a concentration of 28 μg/mL (low-dose), while exposure to a concentration of 56 μg/mL (high-dose) caused a reduction in PANC-1 cell viability to 50% after 72 h by inducing reactive oxygen species (ROS) production, reduced glutathione (GSH) depletion, lipid peroxidation, enhancement of caspase-1 activity, and LDH release. An alteration in Hsp70 and Hsp90 protein expression was also observed. At low doses, these findings provide evidence that DIO-NPs could act as safe platforms in drug delivery, as well as antitumoral and imaging agents for theranostic uses in pancreatic cancer.
氧化铁纳米颗粒是胰腺癌治疗应用中最有前途的工具之一，因为其独特的物理化学和磁性特性使其既适合诊断又适合治疗。因此，我们的研究旨在表征通过共沉淀合成的葡聚糖包覆的磁铁矿（γ-FeO）型氧化铁纳米颗粒（DIO-NPs）的性质，并研究其对胰腺癌细胞的影响（低剂量与高剂量），重点关注 NP 细胞摄取、磁共振对比和毒理学特征。本文还探讨了热休克蛋白（HSPs）和 p53 蛋白表达的调节以及 DIO-NPs 用于治疗应用的潜力。DIO-NPs 的特性通过 X 射线衍射（XRD）、透射电子显微镜（TEM）、动态光散射分析（DLS）和zeta 电位进行表征。胰腺癌细胞（PANC-1 细胞系）暴露于不同剂量的葡聚糖包覆的γ-FeO NPs（14、28、42、56μg/mL）长达 72 小时。结果表明，具有 16.3nm 水动力学直径的 DIO-NPs 使用 7 T MRI 扫描仪产生显著的负对比，与剂量依赖性细胞铁摄取和毒性水平相关。我们表明，DIO-NPs 在 28μg/mL（低剂量）的浓度下是生物相容的，而暴露于 56μg/mL（高剂量）浓度会在 72 小时后通过诱导活性氧（ROS）产生、减少谷胱甘肽（GSH）耗竭、脂质过氧化、增强 caspase-1 活性和 LDH 释放，导致 PANC-1 细胞活力降低至 50%。还观察到 Hsp70 和 Hsp90 蛋白表达的改变。在低剂量下，这些发现为 DIO-NPs 可以作为药物递送的安全平台提供了证据，以及作为胰腺癌治疗应用的抗肿瘤和成像剂。
