Abstract:
This work aimed to prepare a new system for daunorubicin (DNR) delivery to improve therapeutic efficiency and decrease unwanted side effects. Typically, at first, a carboxylic acid functional group containing metal-organic framework (UiO-66-COOH) was synthesized in a simple way. Then, a third generation of citric acid dendrimer (CAD G3) was grown on it (UiO-66-COOH-CAD G3). Finally, the system was functionalized with pre-modified hyaluronic acid (UiO-66-COOH-CAD-HA). SEM analysis displayed that the synthesized particles have a spherical shape with an average particle size ranging from 260 to 280 nm. An increase in hydrodynamic diameter from 223 nm for UiO-66-COOH to 481 nm for UiO-66-COOH-CAD-HA is a sign of success in the performed reactions. Also, the average pore size was calculated at about 4.04 nm. The DNR loading efficiency of UiO-66-COOH-CAD-HA was evaluated at ∼74 % (DNR@UiO-66-COOH-CAD-HA). It was observed that the drug release rate at a lower pH is more than higher pH. The maximum hemolysis of <3 % means that the UiO-66-COOH-CAD-HA is hemocompatible. The use of DNR-loaded UiO-66-COOH-CAD-HA led to cell-killing of 77.9 % for MDA-MB 231. These results specified the great potential of UiO-66-COOH-CAD-HA for tumor drug delivery, so it could be proposed as a new carrier for anticancer agents to minimize adverse effects and improve therapeutic efficacy.
摘要:
这项工作旨在制备一种用于柔红霉素(DNR)递送的新系统,以提高治疗效率并减少不必要的副作用。通常,首先,以简单的方法合成了含羧酸官能团的金属有机骨架(UiO-66-COOH)。然后,在其上生长第三代柠檬酸树枝状聚合物(CADG3)(UiO-66-COOH-CADG3)。最后,该系统用预修饰的透明质酸(UiO-66-COOH-CAD-HA)官能化。SEM分析显示,合成的颗粒具有平均粒度为260至280nm的球形。流体动力学直径从UiO-66-COOH的223nm增加到UiO-66-COOH-CAD-HA的481nm是所进行的反应成功的标志。此外,平均孔径计算为约4.04nm。UiO-66-COOH-CAD-HA的DNR负载效率评估为~74%(DNR@UiO-66-COOH-CAD-HA)。观察到在较低pH下的药物释放速率大于较高pH。<3%的最大溶血意味着UiO-66-COOH-CAD-HA是血液相容性的。使用载有DNR的UiO-66-COOH-CAD-HA导致MDA-MB231的77.9%的细胞杀伤。这些结果说明了UiO-66-COOH-CAD-HA用于肿瘤药物递送的巨大潜力,因此,它可以作为一种新的抗癌药物载体,以减少副作用,提高治疗效果。