MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Biomaterials. 2012 Mar;33(9):2780-90. doi: 10.1016/j.biomaterials.2011.12.035. Epub 2012 Jan 11.
Co-delivery of siRNA and chemotherapeutic agents has been developed to combat multidrug resistance in cancer therapy. Recently, we developed a series of quantum dots (QDs) functionalized by β-cyclodextrin (β-CD) coupled to amino acids, some of which can be used to facilitate the delivery of siRNA. In this study, two CdSe/ZnSe QDs modified with β-CD coupled to L-Arg or L-His were used to simultaneously deliver doxorubicin (Dox) and siRNA targeting the MDR1 gene to reverse the multidrug resistance of HeLa cells. In this co-delivery system, Dox was firstly encapsulated into the hydrophobic cavities of β-CD, resulting in bypass of P-glycoprotein (P-gp)-mediated drug efflux. After complex formation of the mdr1 siRNA with Dox-loaded QDs via electrostatic interaction, significant down-regulation of mdr1 mRNA levels and P-gp expression was achieved as shown by RT-PCR and Western blotting experiments, respectively. The number of apoptotic HeLa cells after treatment with the complexes substantially exceeded the number of apoptotic cells induced by free Dox only. The intrinsic fluorescence of the QDs provided an approach to track the system by laser confocal microscopy. These multifunctional QDs are promising vehicles for the co-delivery of nucleic acids and chemotherapeutics and for real-time tracking of treatment.
载药纳米粒用于克服癌症多药耐药性的研究进展。最近，我们开发了一系列由β-环糊精（β-CD）偶联氨基酸功能化的量子点（QDs），其中一些可用于促进 siRNA 的递送。在本研究中，我们使用两种由 β-CD 偶联 L-Arg 或 L-His 修饰的 CdSe/ZnSe QDs 来同时递送多柔比星（Dox）和针对 MDR1 基因的 siRNA，以逆转 HeLa 细胞的多药耐药性。在这个共递药系统中，Dox 首先被包裹在 β-CD 的疏水腔内，从而绕过 P-糖蛋白（P-gp）介导的药物外排。通过静电相互作用将载 Dox 的 QDs 与 mdr1 siRNA 复合后，RT-PCR 和 Western blot 实验分别显示 mdr1 mRNA 水平和 P-gp 表达显著下调。用复合物处理后的 HeLa 细胞凋亡数量明显超过单独用游离 Dox 诱导的凋亡细胞数量。QDs 的固有荧光为通过激光共聚焦显微镜进行系统追踪提供了一种方法。这些多功能 QDs 是核酸和化疗药物共递药以及实时治疗监测的有前途的载体。
