The novel Apt/CPP‐CPTD NPs selectively accumulated in tumor site via EPR effect and performed increased tumor penetration ability by the exposed CPP, which was activated in the PDAC‐related ECM component tenascin C. After endocytosis, CPTD prodrug could be sequentially triggered by intravenous redox potential and provide controlled drug release. The gene discussed is TNC; the disease is neoplasm.