Henan Province Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences , Zhengzhou University , No. 100 Science Avenue , Zhengzhou , Henan 450001 , P. R. China.
College of Pharmacy , Henan University , Jin Ming Avenue , Kaifeng , Henan 475004 , P. R. China.
Mol Pharm. 2018 Sep 4;15(9):3767-3776. doi: 10.1021/acs.molpharmaceut.8b00046. Epub 2018 Aug 23.
Multidrug resistance (MDR) remains a formidable challenge to effective clinical cancer therapy. Herein, a nonviral gene delivery system HA/anti-miR-21/PPAuNCs to overcome MDR was reported. This system could condense the microRNA-21 inhibitor (anti-miR-21) into hyaluronic acid-conjugated and polyethylenimine-modified PEGylated gold nanocages (AuNCs) and had good stability. In vitro studies demonstrated that HA/anti-miR-21/PPAuNCs could enhance intracellular DOX accumulation in DOX-resistant HCC cells (HepG2/ADR cells) and increase the sensitivity to DOX of HepG2/ADR cells through upregulating PTEN protein expression mediated by anti-miR-21 and downregulating P-gp protein expression mediated by the hyperthermia of HA/PPAuNCs upon mild near-infrared irradiation. Furthermore, the therapeutic effects had been enhanced due to the combination of chemotherapy, gene therapy, and photothermal therapy. Besides, HA/anti-miR-21/PPAuNCs have a good biocompatibility. These findings can provide new insights and strategies for the treatment of cancers with MDR.
多药耐药（MDR）仍然是癌症有效临床治疗的巨大挑战。在此，报道了一种非病毒基因传递系统 HA/抗 miR-21/PPAuNCs 来克服 MDR。该系统可以将 microRNA-21 抑制剂（抗 miR-21）浓缩到透明质酸偶联和聚乙烯亚胺修饰的聚乙二醇化金纳米笼（AuNCs）中，具有良好的稳定性。体外研究表明，HA/抗 miR-21/PPAuNCs 可以通过抗 miR-21 介导的上调 PTEN 蛋白表达和 HA/PPAuNCs 的温和近红外照射诱导的热疗介导的下调 P-糖蛋白蛋白表达，增强多柔比星耐药 HCC 细胞（HepG2/ADR 细胞）中的 DOX 细胞内积累，并增加 HepG2/ADR 细胞对 DOX 的敏感性。此外，由于化疗、基因治疗和光热治疗的结合，治疗效果得到了增强。此外，HA/抗 miR-21/PPAuNCs 具有良好的生物相容性。这些发现可为治疗 MDR 癌症提供新的见解和策略。
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