PDGFRβ-specific affibody-directed delivery of a photosensitizer, IR700, is efficient for vascular-targeted photodynamic therapy of colorectal cancer

AbstractVascular-targeted photodynamic therapy (PDT) is an important strategy for cancer therapy. Conventional vascular-targeted PDT has been achieved by passive photosensitizer (PS) delivery, which involves a high risk of adverse effects. Active PS delivery is urgently required for vascular-targeted PDT. Although endothelial cells and pericytes are major cellular components of tumor blood vessels, little attention has been paid to pericyte-targeted PDT for cancer therapy. PDGFRβ is abundantly expressed in the pericytes of various tumors. In this experiment, a dimeric ZPDGFRβ affibody with a 0.9 nM affinity for PDGFRβ was produced. The ZPDGFRβ affibody showed PDGFRβ-dependent pericyte binding. Intravenously injected ZPDGFRβ affibody was predominantly distributed on pericytes and thus accumulated in LS174T tumor grafts. The conjugate of the ZPDGFRβ affibody and IR700 dye, i.e. ZIR700, bound to PDGFRβ+ pericytes but not to PDGFRβ− LS174T tumor cells. Accordingly, ZIR700-mediated PDT in vitro induced the dea...