CXCR4 and neoplasm: By using multi‐functionalized nano‐systems with the delivery vector composed of histone for plasmids loading, hyaluronic acid for tumor targeting, and a fusion peptide for C‐X‐C motif chemokine receptor 4 (CXCR4) targeting as well as nuclear localization, the reprogramming of circulating tumor cells (CTCs) with in situ detection on biomarkers at the single‐cell level is realized.