Improved tumor homing of nanoworms coated with an N-methylated CREKA peptide analog. Nanoworms coated with FAM-labeled CREKA peptide or its N-methylated variant, CR(NMe)EKA, were injected intravenously into mice bearing 22Rv1 tumors (total dose 5 mg of iron per 1 kg). (A) Tumors were harvested 5 hours later, and tumor sections were stained with antibodies and examined by confocal microscopy. CR(NMe)EKA-NWs are green; blood vessels and clotting were visualized separately with anti-CD31 or anti-fibrin(ogen) staining (red). Nuclei were stained with DAPI (blue). Bars represent 100 μm (50 μm in the inset). (B) T2-weighted magnetic resonance images (fast spin echo, repetition time = 6.4 seconds, echo time = 69 ms). CREKA-NWs or CR(NMe)EKA-NWs were injected intravenously into tumor-bearing mice. The particles were allowed to circulate for 7-8 hours (the time determined in preliminary experiments to be optimal for differential homing). Gray-scale images of axial planes through the tumors are shown. Gadolinium (Gd) and Feridex (iron) were used as reference standards. n = 3-4.