Recombinant nanocomposites by the clinical drugs of Abraxane® and Herceptin® as sequentially dual-targeting therapeutics for breast cancer

Breast cancer greatly threatens the health of women all over the word despite of several effective drugs. Targeted therapy for breast cancer is limited to human epidermal growth factor receptor 2 (HER2). Herceptin (R), monoclonal antibody against HER2, is now widely used in HER2(+) breast cancer. Abraxane (R), the current gold standard for paclitaxel (PTX) delivery, has shown superiority in breast cancer based on nanoparticle albumin bound technology. Despite these advances, further novel targeted therapy with more improved anti-tumor efficacy for breast cancer is still urgently needed. Here, we report the recombinant nanocomposites (NPs) composed of the above two clinical drugs of Abraxane (R) and Herceptin (R) (Abra/anti-HER2), which at first migrates to the tumor region through the unique targeting mechanism of human serum albumin (HSA) of Abraxane (R), and sequentially further precisely recognize the HER2(+) breast cancer cells due to Herceptin (R). The Abra/anti-HER2 NPs were fabricated by a "one-step" synthesis using EDC/NHS. In vitro analysis of cell viability, apoptosis and cell cycle revealed that Abra/anti-HER2 NPs showed more anti-tumor efficacy against HER2(+) SK-BR-3 cells than Abraxane (R) at equivalent PTX concentration. In addition, in HER2(+) breast cancer xenograft model, Abra/anti-HER2 NPs significantly inhibited tumor growth with less side effects. Moreover, the properties of more precise target and delayed release of PTX were proved by NIRF imaging. Thus, our results indicate that Abra/anti-HER2 NPs could represent a next-generation sequentially dual-targeting therapeutic agent for HER2(+) breast cancer.