在这项研究中，我们通过冻干法制备了β-环糊精聚合物（β-CDP）共载有槲皮素（QCT）和多柔比星（DOX）的纳米载体（β-CDP/QD NCs），以对抗KB-ChR 8-5癌细胞中的P-糖蛋白介导的多药耐药（MDR）。采用各种显微镜和光谱技术对制备的纳米载体进行表征。分子对接研究确认了QCT和DOX与合成的β-CD聚合物之间的有效结合相互作用。体外药物释放研究说明了β-CDP纳米载体可持续地释放DOX和QCT。此外，我们发现β-CDP纳米载体中释放的QCT通过调节KB-ChR 8-5细胞和MCF-7/DOX癌细胞中的P-糖蛋白药物外排功能，提高了DOX的细胞内可用性。细胞摄取结果证实了KB-ChR 8-5细胞与游离DOX相比成功地摄取了DOX。细胞基于核的浓缩、线粒体膜电位（MMP）的改变以及凋亡形态学变化等细胞基于的实验，确认了β-CDP/QD NCs在耐药癌细胞中的增强抗癌作用。因此，共载有QCT和DOX的β-CDP可被认为是在P-糖蛋白过表达的MDR癌细胞中实现最大细胞死亡的有效方法。版权所有©2023 Elsevier B.V.。

In this study, we prepared a β-cyclodextrin polymer (β-CDP) co-loaded quercetin (QCT) and doxorubicin (DOX) nanocarrier (β-CDP/QD NCs) by freeze-dried method to combat P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in KB-ChR 8-5 cancer cells. Various microscopic and spectroscopic techniques were employed to characterize the prepared nanocarrier. The molecular docking studies confirm the effective binding interactions of QCT and DOX with the synthesized β-CD polymer. The in vitro drug release study illustrates the sustainable release of DOX and QCT from the β-CDP nanocarrier. Further, we noticed that the QCT released from the β-CDP nanocarrier improved the intracellular availability of DOX via modulating P-gp drug efflux function in KB-ChR 8-5 cells and MCF-7/DOX cancer cells. Cell uptake results confirmed the successful internalization of DOX in KB-ChR 8-5 cells compared with free DOX. Cell-based assays such as nuclear condensation, alteration in the mitochondrial membrane potential (MMP), and apoptosis morphological changes confirmed the enhanced anticancer effect of β-CDP/QD NCs in the resistant cancer cells. Hence, QCT and DOX co-loaded β-CDP may be considered effective in achieving maximum cell death in the P-gp overexpressing MDR cancer cells.Copyright © 2023 Elsevier B.V. All rights reserved.