Abstract：
This study aims to investigate the molecular mechanisms and the neuroprotective effect of hyaluronic acid modified verapamil-loaded carbon quantum dots (VRH-loaded HA-CQDs) against an in-vitro Alzheimer\'s disease model induced by amyloid beta (Aβ) in SH-SY5Y and Neuro 2a neuroblastoma cells. Briefly, different HA-CQDs were prepared using hydrothermal method and optimized by Box-Behnken design to maximize quantum yield and minimize particle size. Serum stable negatively charged VRH-loaded HA-CQDs was successfully prepared by admixing the optimized HA-CQDs and VRH with association efficiency and loading capacity of 81.25 ± 3.65 % and 5.11 ± 0.81 %, respectively. Cells were pretreated with VRH solution or loaded-HA-CQDs followed by exposure to Aβ. Compared to the control group, amyloidosis led to reduction in cellular proliferation, mitochondrial membrane potential, expression of cytochrome P450, cytochrome c oxidase, CREB-regulated transcriptional coactivator 3, and mitotic index, along with marked increase in reactive oxygen species (ROS) and inflammatory cytokines. Pretreatment with VRH, either free or loaded HA-CQDs, enhanced cell survival, mitochondrial membrane potential, mitotic index, and gene expression. It also reduced inflammation and ROS. However, VRH-loaded HA-CQDs exhibited superior effectiveness in the measured parameters. These findings suggest that VRH-loaded HA-CQDs have enhanced therapeutic potential compared to free VRH in mitigating amyloidosis negative features.
摘要：
本研究旨在探讨透明质酸修饰的维拉帕米碳量子点（VRH负载HA-CQDs）对SH-SY5Y和Neuro2a神经母细胞瘤细胞中淀粉样β（Aβ）诱导的阿尔茨海默病模型的分子机制和神经保护作用。简而言之，使用水热法制备不同的HA-CQD，并通过Box-Behnken设计进行优化，以最大化量子产率并最小化粒径。通过混合优化的HA-CQDs和VRH，成功制备了血清稳定的带负电荷的VRH负载HA-CQDs，缔合效率和负载能力分别为81.25±3.65％和5.11±0.81％，分别。用VRH溶液或负载的HA-CQD预处理细胞,然后暴露于Aβ。与对照组相比,淀粉样变性导致细胞增殖减少，线粒体膜电位，细胞色素P450，细胞色素C氧化酶，CREB调节的转录共激活因子3和有丝分裂指数，随着活性氧（ROS）和炎症细胞因子的显着增加。用VRH预处理,免费或加载的HA-CQD，增强细胞存活,线粒体膜电位，有丝分裂指数,和基因表达。它还减少炎症和ROS。然而,VRH负载的HA-CQD在测量参数中表现出优异的有效性。这些发现表明，与游离VRH相比，VRH负载的HA-CQD在减轻淀粉样变性阴性特征方面具有增强的治疗潜力。
