In particular, using the unique HER2-positive tumor of BALB/c mice developed by us in this work, we demonstrate that the developed two-step DDS based on barnase/barstar showed superior efficiency in image-guided cancer therapy: HER2-positive tumors’ treatment tests showed the tumor growth inhibition index TGI = 68.4% for one-step DDS and TGI = 94.9% for two-step DDS. This evidence concerns the gene ERBB2 and cancer.