Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Dec;394(12):2353-2362. doi: 10.1007/s00210-021-02152-9. Epub 2021 Sep 15.
Resistance to chemotherapeutic drugs is the main limitation of cancer therapy. The combination use of chemotherapeutic agents and galangin (a naturally active flavonoid) amplifies the effectiveness of cancer treatment. This study aimed to prepare arginyl-glycyl-aspartic acid (RGD) containing nanostructured lipid carrier (NLC-RGD) to improve the bioavailability of galangin and explore its ability in improving the cytotoxic effects of doxorubicin (DOX). Galangin-loaded NLC-RGD was prepared by hot homogenization method and characterized by diverse techniques. Then, cytotoxicity, uptake, and apoptosis induction potential of prepared nanoparticles beside the DOX were evaluated on A549 lung cancer cells. Finally, the expression level of some ABC transporter genes was evaluated in galangin-loaded NLC-RGD-treated cells. Nanoparticles with appropriate characteristics of the delivery system (size: 120 nm, polydispersity index: 0.23, spherical morphology, and loading capacity: 59.3 mg/g) were prepared. Uptake experiments revealed that NLC-RGD promotes the accumulation of galangin into cancerous cells by integrin-mediated endocytosis. Results also showed higher cytotoxicity and apoptotic effects of DOX + galangin-loaded NLC-RGD in comparison to DOX + galangin. Gene expression analysis demonstrated that galangin-loaded NLC-RGD downregulates ABCB1, ABCC1, and ABCC2 more efficiently than galangin. These findings indicated that delivery of galangin by NLC-RGD makes it an effective adjuvant to increase the efficacy of chemotherapeutic agents in cancer treatment.
化疗药物耐药性是癌症治疗的主要限制因素。化疗药物与姜黄素（一种天然活性类黄酮）联合使用可提高癌症治疗的效果。本研究旨在制备精氨酸-甘氨酸-天冬氨酸（RGD）载纳米结构脂质载体（NLC-RGD）以提高姜黄素的生物利用度，并探讨其提高阿霉素（DOX）细胞毒性作用的能力。采用热匀相法制备姜黄素载 NLC-RGD，并通过多种技术进行表征。然后，在 A549 肺癌细胞上评估了制备的纳米粒子对 DOX 的细胞毒性、摄取和诱导细胞凋亡的能力。最后，评估了姜黄素载 NLC-RGD 处理细胞中某些 ABC 转运体基因的表达水平。制备了具有适当递药系统特性的纳米粒子（粒径：120nm，多分散指数：0.23，球形形态，载药量：59.3mg/g）。摄取实验表明，NLC-RGD 通过整合素介导的内吞作用促进姜黄素进入癌细胞。结果还表明，与 DOX+姜黄素相比，DOX+姜黄素载 NLC-RGD 具有更高的细胞毒性和促凋亡作用。基因表达分析表明，与姜黄素相比，NLC-RGD 载姜黄素能更有效地下调 ABCB1、ABCC1 和 ABCC2。这些发现表明，NLC-RGD 递姜黄素可作为一种有效的佐剂，提高化疗药物在癌症治疗中的疗效。
