Nanoworm distribution and effects on intravascular clotting, tumor apoptosis, and tumor therapy. Mice bearing 2-week-old orthotopic xenografts of 22Rv1 human prostate cancer were injected intravenously with nanoworms coated with peptides through a 5-kDa PEG spacer. The nanoworms were administered every other day for 14 days (5 mg of iron per kilogram per day, total cumulative dose 35 mg/kg). (A) Tumor sections were stained with anti-CD31 (red); CR(NMe)EKA-NW/CRKDKC-NW combination is shown as green; nuclei were stained with DAPI (blue). Bars represent 200 μm. The necrotic area at the center of the tumor is autofluorescent. (B) CEUS imaging and analysis showed reduction in tumor blood flow at the end of treatment. The images are representative of n = 3. (C) Staining with hematoxylin and eosin showed a large necrotic area (arrow) in the middle of a typical tumor treated with the CR(NMe)EKA-NW/CRKDKC-NW combination and occluded vessels in the viable rim of these tumors (broken arrows). A tumor of a similar size from a mouse treated with CRKDKC-NWs alone is shown for comparison. (D) Apoptosis analysis by TUNEL staining is shown as red; nanoworm combination is shown as green; nuclei were stained with DAPI. Bars represent 200 μm.