Selectively Suppressing Tumor Angiogenesis for Targeted Breast Cancer Therapy by Genetically Engineered Phage

Antiangiogenesis is a promising approach to cancer therapy but is limited by the lack of tumor-homing capability of the current antiangiogenic agents. Angiogenin, a protein overexpressed and secreted by tumors to trigger angiogenesis for their growth, has never been explored as an antiangiogenic target in cancer therapy. Here it is shown that filamentous fd phage, as a biomolecular biocompatible nanofiber, can be engineered to become capable of first homing to orthotopic breast tumors and then capturing angiogenin to prevent tumor angiogenesis, resulting in targeted cancer therapy without side effects. The phage is genetically engineered to display many copies of an identified angiogenin-binding peptide on its side wall and multiple copies of a breast-tumor-homing peptide at its tip. Since the tumor-homing peptide can be discovered and customized virtually toward any specific cancer by phage display, the angiogenin-binding phages are thus universal "plug-and-play" tumor-homing cancer therapeutics.