Hierarchical Drug Release Designed Au @PDA-PEG-MTX NPs for Targeted Delivery to Breast Cancer with Combined Photothermal-chemotherapy

Abstract

Breast cancer (BC) is the frequently diagnosed cancer and one of the deadliest causes of cancer-related death with a severe survival rate. Methotrexate (MTX) is an anti-tumor drug used in the treatment of BC. The poor dispersion in water and toxic side effects limit its clinical application. Gold nanoparticles (AuNPs), due to their specific structures and unique biological and physiochemical properties, have emerged as attractive candidates as vehicles for tumor targeting, bio-imaging and therapy. An innovative nano drug-loading system (Au @PDA-PEG-MTX NPs) was prepared for targeted treatment of BC. Au @PDA-PEG-MTX NPs under near infra-red region (NIR) irradiation showed effective photothermal therapy against MDA-MB-231 human BC cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and generating excessive heat. In vivo studies revealed that Au @PDA-PEG-MTX NPs under NIR irradiation showed deep penetration and cancer-targeted fluorescence imaging application and strong photothermal therapy against BC xenograft growth in vivo by induction of apoptosis. Analysis of histopathology, cellular uptake, cytotoxicity assay, apoptosis experiment indicated that Au @PDA-PEG-MTX NPs had a good therapeutic effect with high biocompatibility and less side effect. This Au NPs drug-loading system achieved specific BC targeting ability by surface decoration of MTX, NIR laser irradiation for fluorescence imaging and combined photothermal-chemotherapy as well as pH- and NIR- triggered hierarchical drug release.