In this study, we identified a NSCLC-targeting peptide and demonstrated its improved therapeutic efficiency in animal models. Specifically, we found a phage clone PC5-2 that made up 90% of the selected phages binding to CL1-5 cells after five rounds of biopanning (Table 1) . Immunohistochemistry and flow cytometry assays confirmed that PC5-2 bound to NSCLC cell surface. The same binding results were observed in the cognate synthetic peptide SP5-2, which replaced PC5-2 ( Fig. 1 and Figs. S1, S2, S3). These experiments supported that this targeting peptide can specifically bind to the cell surface of NSCLC cell lines. In vivo experiments also consolidated the homing ability of the peptide. The expression of the SP5-2 peptide (TDSILR-SYDWTY) guides the phage to accumulate in NSCLC xenografts but not in normal organs (Fig. 2) . The binding activity of PC5-2 to tumor tissues was inhibited by the synthetic peptide SP5-2 (Fig. 2B) , indicating that PC5-2 interacted with NSCLC cells by its displayed peptide and not by another part of the phage particle. That the mutated synthetic peptide, MP5-2, did not inhibit the PC5-2 binding demonstrated the importance of the WTY motif in the binding activity (Fig. 2B) . Moreover, this phenomenon was observed in immunohistochemical staining of surgical specimens from human lung cancer (Fig. 1D e and f) , in animal models for ligand-targeted chemotherapy (Fig. 3A) and in tumor localization of doxorubicin delivered by SP5-2-conjugated targeting liposomes (Figs. 4 and 5A) .