Department of Pediatrics, Rizhao People's Hospital, Shandong, China.
Aging (Albany NY). 2020 Apr 7;12(7):6018-6029. doi: 10.18632/aging.102992.
To ameliorate multidrug resistance (MDR) observed in leukemia cells, nanomicelles modified by transferrin (Tf-M-DOX/PSO), coencapsulating doxorubicin (DOX) and psoralen (PSO), were designed, synthesized and tested in K562 and doxorubicin-resistant K562 (K562/DOX) cells. drug release kinetics for constructed nanomicelles were measured using high-performance liquid chromatography. Characterization of the produced nanomicelles was completed using transmission electron microscopy and dynamic light scattering. Uptake of the nanomicelles in K562 cells was investigated using both confocal microscopy and flow cytometry. Apoptosis levels as well as the expression of glycoprotein (P-gp) were analyzing by western blotting and flow cytometry. Cellular cytotoxicity resulting from the exposure of nanomicelles was evaluated using MTT assays. The nanomicelles all showed mild release of DOX in PBS solution. In K562/DOX cells, Tf-M-Dox/PSO exhibited higher uptake compared to the other nanomicelles observed. Furthermore, cellular cytotoxicity when exposed to Tf-M-Dox/PSO was 2.8 and 1.6-fold greater than observed in the unmodified DOX and Tf-nanomicelles loaded with DOX alone, respectively. Tf-M-Dox/PSO strongly increased apoptosis of K562/DOX cells. Finally, the reversal of the drug resistance when cells are exposed to Tf-M-DOX/PSO was associated with P-gp expression inhibition. The Tf-M-Dox/PSO nanomicelle showed a reversal of MDR, with enhanced cellular uptake and delivery release.
为了改善白血病细胞中观察到的多药耐药性（MDR），设计、合成并在 K562 和多柔比星耐药 K562（K562/DOX）细胞中测试了转铁蛋白（Tf）修饰的载多柔比星和补骨脂素的纳米胶束（Tf-M-DOX/PSO），共包载多柔比星（DOX）和补骨脂素（PSO）。采用高效液相色谱法测定构建的纳米胶束的药物释放动力学。采用透射电子显微镜和动态光散射对所制备的纳米胶束进行了表征。通过共聚焦显微镜和流式细胞术研究了纳米胶束在 K562 细胞中的摄取情况。采用 Western blot 和流式细胞术分析了细胞凋亡水平和糖蛋白（P-gp）的表达。采用 MTT 法评估纳米胶束暴露后产生的细胞毒性。纳米胶束在 PBS 溶液中均表现出 DOX 的温和释放。在 K562/DOX 细胞中，Tf-M-Dox/PSO 的摄取量高于其他观察到的纳米胶束。此外，与单独负载 DOX 的未修饰 DOX 和 Tf 纳米胶束相比，Tf-M-Dox/PSO 暴露时细胞毒性分别增加了 2.8 倍和 1.6 倍。Tf-M-Dox/PSO 可显著增加 K562/DOX 细胞的凋亡。最后，当细胞暴露于 Tf-M-DOX/PSO 时，药物耐药性的逆转与 P-gp 表达抑制有关。Tf-M-Dox/PSO 纳米胶束表现出逆转 MDR 的作用，具有增强的细胞摄取和递药释放。
