Trastuzumab is the first approved monoclonal antibody against human epidermal growth receptor-2 (HER-2) breast cancer. This antibody significantly limits the therapeutic results. Thus, tumour microenvironment (TME) pH-responsive nanoparticles have been developed to deliver systemic mRNAs to reverse the trastuzumab resistance of breast cancer. This evidence concerns the gene ERBB2 and breast cancer.