A stimuli-responsive NG crosslinked via a matrix metalloproteinase (MMP-2/9) substrate and armed with 5-[125I] iodo-4′-thio-2′′-deoxyuridine ([125I]ITdU) (Auger electron-emitting drug), and post modified by the surface functionalization with diphtheria toxin receptor (DTR) ligand cross-reactive material 197 (CRM-197), was fabricated for allowing the transcytosis across the BBB at the tumor site. Here, HBEGF is linked to neoplasm.