Hyaluronic Acid-Functionalized Gold Nanorods with pH/NIR Dual-Responsive Drug Release for Synergetic Targeted Photothermal Chemotherapy of Breast Cancer

Tumor-targeted delivery of photothermal agent and controlled release of concomitant chemotherapeutic drug are two key factors for combined photothermal chemotherapy. Herein, we developed a pH/near-infrared (NIR) dual-triggered drug release nanoplatform based on hyaluronic acid (HA)-functionalized gold nanorods (GNRs) for actively targeted synergetic photothermal chemotherapy of breast cancer. Targeting folate (FA), dopamine, and adipic acid dihydrazide triconjugated HA was first synthesized and used to decorate GNRs via Au-catechol bonds, and then an anticarcinogen doxorubicin (DOX) was conjugated onto HA moieties via an acid-labile hydrazone linkage, resulting in multifunctional nanoparticles GNRs-HA-FA-DOX. The nanoparticles exhibited excellent stability and had a pH and NIR dual-responsive drug release behavior. In vitro studies showed that the nanoparticles could be efficiently internalized into breast cancer MCF-7 cells and kill them under NIR irradiation in a synergistic fashion via inducing cell apoptosis. Pharmacokinetics and biodistribution studies in tumor-bearing mice indicated that the nanoparticles had a long blood circulation with a half-life of 2.4 h and exhibited a high accumulation of 11.3% in tumor site. The tumors of mice treated with combined chemotherapy and photothermal therapy were completely suppressed without obvious systemic toxicity after 20 d of treatment. These results demonstrated a great potential of GNRs-HA-FA-DOX nanoparticles for targeted synergistic therapy of breast cancer.