Reverse Multidrug Resistance in Human HepG2/ADR by Anti-miR-21 Combined with Hyperthermia Mediated by Functionalized Gold Nanocages

ABSTRACT: Multidrug resistance (MDR) remains a formidable challenge to effective clinical cancer therapy. Herein, a non-viral gene delivery system HA/anti-miR-21/PPAuNCs to overcome MDR was reported. This system could condense microRNA-21 inhibitor (anti-miR-21) into hyaluronic acid (HA)-conjugated and polyethyleneimine (PEI)-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 upregulating P-gp protein expression mediated by the hyperthermia of HA/PPAuNCs upon mild near infrared (NIR) irradiation. Furthermore, the therapeutic effects had been enhanced due to the combination of chemotherapy, gene therapy, and photothermal therapy (PTT). Besides, HA/anti-miR-21/PPAuNCs had good biocompatibility. These findings would provid...