论文部分内容阅读
The objective of the research is to develop a targeted laser-activatable photodynamic therapy by selective and effective targeting of tumor blood vessels and tumor cells via binding an angiogenic receptor tissue factor using its natural ligand factor Ⅶ.The cell surface receptor tissue factor (TF) is a common but specific target on angiogenic tumour vascular endothelial cells (VECs) and tumour cells.We have previously developed a TF-targeting Icon (a dimeric factor Ⅶ/IgG1 Fc) immunotherapy for eradication of pathological neovasculature for treatment of cancer(1-3), macular degeneration(4), and endometriosis(5).Here we report for the first time the development of another novel and effective ligand-targeted photodynamic therapy (tPDT) for eradication of breast cancer by conjugating monomeric fⅦ protein to photosensitiser Sn(Ⅳ) chlorin e6.Our results show that fVII-tPDT not only enhances the effect of nontargeted PDT but also can selectively kill cancer cells and angiogenic VECs in vitro.Furthermore, we demonstrate that fVII-tPDT is efficacious for eradication of murine and human breast cancer in mice.fⅦ-tPDT could have broad therapeutic potential for breast cancer and other cancers in which TF expression is detected on tumour VECs and/or tumour cells.