Marriage of antibody–drug conjugate with gold nanorods to achieve multi-modal ablation of breast cancer cells and enhanced photoacoustic performance

Abstract

Her2-positive breast cancer accounts for 20–25% of the breast cancer population with lower survival rate and higher recurrence risk than non-Her2-positive breast cancer. The recent approval of trastuzumab emtansine (T-DM1), an antibody–drug conjugate, significantly improves therapeutic outcomes of Her2-positve breast cancer. In this report, we designed and fabricated a novel nanodrug taking advantage of T-DM1 and mesoporous silica coated gold nanorods (GNR@mSiO₂) to integrate multiple functions of active targeting, antibody therapy, drug therapy and photothermal therapy (PTT) within one single platform to fight against Her2-positive breast cancer. The engineered nanodrug (GNR@mSiO₂–TDM1) has accelerated cell surface binding and internalization compared to the intact drug T-DM1, which allows fast action of the drug. GNR@mSiO₂–TDM1 specifically ablated Her2-positive breast cancer cells in vitro through multi-modal treatment with enhanced efficiency. In addition, the engineered nanodrug has amplified photoacoustic performance allowing sensitive detection of Her2-positive cancer cells. This represents a significant finding since, up to now, only reduced graphene oxide and silica have been found to enhance the photoacoustic performance of gold nanorods. These findings have clinical implications to deal with the troubling issues of current cancer therapy. Targeted multi-modal ablation of breast cancer cells would greatly facilitate the treatment safety and efficiency, and would be of particular value in the emerging era of personalized medicine.