PDF(Pubmed)
Abstract：
The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier\'s surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.
摘要：
G4.0PAMAM树枝状聚合物的独特结构允许药物被封闭在内部空间或固定在表面上。在进行的研究中，优化了与盐酸多柔比星（DOX）形成活性G4.0PAMAM复合物的条件。使用动态光散射（DLS）监测系统的物理化学性质，圆二色性（CD），和荧光光谱。选择具有耗散监测的石英晶体微天平(QCM-D)方法来确定络合物形成的优选条件。当DOX分子去质子化时,在碱性条件下观察到药物与阳离子树枝状聚合物的最高结合效率。络合物的ζ电位的降低证实了DOX通过与载体的表面胺基的静电相互作用而固定。结合常数由在G4.0PAMAM存在下DOX分子的荧光猝灭确定。在等温量热法（ITC）等温线中可见树枝状分子结构中结合阿霉素的双重方式。荧光光谱和释放曲线确定了DOX与纳米载体的可逆结合。在选定的癌细胞中，在A375恶性黑色素瘤细胞中观察到G4.0-DOX复合物最有希望的抗癌活性。此外，发现了有关游离药物的复合物的优选细胞内位置，从治疗的角度来看，这是必不可少的。
