Reverse Multidrug Resistance in Human HepG2/ADR by Anti-miR-21 Combined with Hyperthermia Mediated by Functionalized Gold Nanocages.
Weiping WangShengnan HuangJinxiu YuanXin XuHuili LiZhanwei LvWei YuShaofeng DuanYurong HuPublished in: Molecular pharmaceutics (2018)
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.
Keyphrases
- cell proliferation
- long non coding rna
- long noncoding rna
- induced apoptosis
- cell cycle arrest
- cancer therapy
- multidrug resistant
- gene therapy
- drug delivery
- adverse drug
- endoplasmic reticulum stress
- cell death
- pi k akt
- signaling pathway
- copy number
- transcription factor
- high resolution
- quantum dots
- electronic health record
- smoking cessation
- induced pluripotent stem cells