A Multi-Targeted Drug Delivery Vehicles for Dual Chemo- and Photothermal HER2+ Breast Cancer Therapy

Eradication of breast cancer cells via targeted, triggered release, or thermal ablation methods remains a challenge in the clinic. One dimensional approaches suffer from reoccurence, chemoresistance, and/or toxicity, which warrants the design of a novel, multi-targeted therapeutic with an improved therapeutic index. Here, we synthesized a drug delivery vehicle encapsulating doxorubicin (Dox) within a pH-sensitive matrix, embedded gold (Au) nanoparticles within the interior, and decorated the surface with an antibody for human epidermal growth factor receptor-2 (anti-HER2, Herceptin^®). The pH-responsive matrix entrapped Dox, achieving greater than 70% encapsulation efficiency. Our multi-targeted nanocarrier enhanced specific binding and tumoricidal efficacy in a HER2 overexpressing cell line, SK-BR-3, relative to MCF-7 cells. We demonstrated that multiple modes of targeting were complementary and have potential for use as a cancer therapy.