Department of Physiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
Department of Molecular Biology and Genetics, Hamidiye Institute of Health Sciences, University of Health Sciences-Turkey, Istanbul, Turkey.
Mol Cell Biochem. 2023 Aug;478(8):1813-1824. doi: 10.1007/s11010-022-04632-9. Epub 2022 Dec 27.
Gold nanoparticles (GNPs) have been widely used in medicine such as imaging, drug delivery and therapeutics due to their multifunctional properties. Alterations in neuronal function may contribute to various neurological diseases. Transferrin plays a primary role in iron transportation and delivery and has recently been utilized for drug delivery to the brain. We have investigated effects of transferrin-conjugated GNPs (Tf-GNPs) on anxiety and locomotor behavior in vivo and also hippocampal neuronal activity ex vivo. Electrophysiological effects of Tf-GNP on hippocampal neurons were determined by patch clamp method. Fifteen male young adult C57BL/6 mice were randomly divided into three groups as control (200 µL PBS), GNP (bare GNP; 2.2 μg/g in PBS) and Tf-GNPs (2.2 μg/g Tf-GNP). Animals intraperitoneally received the respective treatments for seven consecutive days and were subjected to elevated plus maze (EPM) and open field tests (OFT). Ex vivo, firing frequency of the neurons significantly increased by GNP treatment (p < 0.001). In vivo, animals in Tf-GNP group showed significantly longer distance in open arms but significantly lower number of entries to the open arms in EPM (p < 0.05). Mice received bare GNPs had significantly higher locomotor activity in OFT (p < 0.05), while Tf-GNP did not alter the locomotor activity significantly (p = 0.051). Animals in Tf-GNP group spent significantly longer time in the peripheral zone in OFT (p < 0.05). The present findings have shown that Tf-GNP induces anxiety-like behavior without altering spontaneous firing rate of hippocampal neurons. We suggest that neurobiological effects of Tf-GNP should be pre-determined before using in medical applications.
金纳米颗粒（GNPs）由于其多功能特性，已广泛应用于医学成像、药物输送和治疗等领域。神经元功能的改变可能导致各种神经疾病。转铁蛋白在铁的运输和输送中起主要作用，最近已被用于将药物递送到大脑。我们研究了转铁蛋白偶联的 GNPs（Tf-GNPs）对体内焦虑和运动行为的影响，以及离体海马神经元活性。通过膜片钳方法确定 Tf-GNP 对海马神经元的电生理效应。15 只雄性年轻成年 C57BL/6 小鼠随机分为三组：对照组（200μL PBS）、GNP（裸 GNP；PBS 中的 2.2μg/g）和 Tf-GNPs（2.2μg/g Tf-GNP）。动物连续 7 天腹腔内接受各自的治疗，然后进行高架十字迷宫（EPM）和旷场测试（OFT）。在离体实验中，GNP 处理使神经元的放电频率显著增加（p<0.001）。在体内，Tf-GNP 组的动物在 EPM 中开放臂的距离明显延长，但进入开放臂的次数明显减少（p<0.05）。接受裸 GNP 的小鼠在 OFT 中的运动活性显著增加（p<0.05），而 Tf-GNP 对运动活性没有显著影响（p=0.051）。Tf-GNP 组的动物在 OFT 中在周边区域停留的时间明显延长（p<0.05）。本研究结果表明，Tf-GNP 诱导焦虑样行为，而不改变海马神经元的自发放电率。我们建议，在将 Tf-GNP 用于医学应用之前，应预先确定其神经生物学效应。
