Dual targeted and pH-responsive gold nanorods with improved chemotherapy and photothermal ablation for synergistic cancer treatment

Abstract

Cancer is considered to be one of the leading causes of morbidity and mortality worldwide. A multifunctional nanosystem based on gold nanorods (GNRs) has demonstrated the potential to enhance therapeutic performance. In this research, dual-targeted pH-responsive GNRs for synergistic cancer treatment were developed and investigated. The GNRs could target angiogenic endothelial cells in the tumor region using αvβ3-mediated recognition and subsequently facilitate its specific binding to tumor cells mediated via recognition of the folate receptor, which could accumulate precisely at the tumor site. Doxorubicin (DOX) was loaded on to the surface of GNRs via a pH-sensitive hydrazone (hz) bond, which could effectively control the drug release by responding to the tumor acidic microenvironment. In vitro, the FA/RGD-DOX-hz-GNRs showed higher tumor specificity and killing ability under near-infrared irradiation. Furthermore, in B16-F10 xenograft tumor-bearing mice, FA/RGD-DOX-hz-GNRs produced the optimal tumor therapeutic efficacy by antagonizing angiogenesis, inhibiting cell proliferation and causing necrosis. Therefore, the strategy of integration of a photothermal effect, chemotherapy and a molecular active targeting based double-targeting mode appeared advantageous over chemotherapy or a photothermal therapy alone.