Small-molecule inhibitor 9 (SMI#9)–gold nanoparticle (GNP) treatment inhibits melanoma growth and lung metastasis. M14 cells were bilaterally implanted subcutaneously in the flanks, and when the tumors reached approximately 150 mm3, mice were randomly assigned to vehicle control, SMI#9, SMI#9-GNP, or blank-GNP group. Mice were treated twice weekly with SMI#9 (or vehicle) administered intratumorally or SMI#9-GNP (or blank-GNP) administered intraperitoneally. A: Tumor volumes. B: Vertical scatter plots of mass of excised tumors at the time of sacrifice at 37 to 44 days. Data were analyzed by one-way analysis of variance and two-tailed t test. C: Representative excised tumors. D: Lungs from control, SMI#9, and SMI#9-GNP–treated mice. D: Arrow shows a pigmented metastatic lesion on the surface of control lungs. E: Top panel: Metastatic melanoma in control tumor-bearing lung tissue revealed by hematoxylin and eosin staining (arrow). Bottom panel: The enlarged image of the metastatic lesion. F: Quantification of metastatic foci detected on surface of lungs in control and treated mice. Results are expressed as means ± SD (A and F). N = 3 (F). ∗∗P < 0.01, ∗∗∗P < 0.001. Original magnification, ×10 (E, top panel).