Dual-targeted therapy in HER2-positive breast cancer cells with the combination of carbon dots/HER3 siRNA and trastuzumab

摘要

Dual-targeted therapy in HER2-positive breast cancer cells with the combination of carbon dots/HER3 siRNA and trastuzumab resulted in enhanced antitumor activity, which overcomes the resistance to trastuzumab monotherapy. Herein, we have developed branched polyethylenimine-functionalized carbon dot (BP-CD) nanocarriers, which exhibited efficient green fluorescent protein gene delivery and expression. The positively charged BP-CDs allowed for effective nucleic acid binding and displayed a highly efficient small interfering RNA (siRNA)-mediated delivery targeting of cancer cells. The transfection of BP-CDs and HER3 siRNA complexes down-regulated HER3 protein expression and induced significant cell growth inhibition in BT-474 cells. BP-CDs/HER3 siRNA complexes induced cell death of BT-474 cells through G0/G1 cell cycle arrest and apoptosis. The combined treatment of BP-CDs/HER3 siRNA complexes and trastuzumab caused greater cell growth suppression in BT-474 cells when compared to either agent alone. The findings suggest that this dual-targeted therapy with the combination of BP-CDs/HER3 siRNA and trastuzumab represents a promising approach in breast cancer.