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

• Main Authors: Qiuxiao Shi, Ze Tao, Hao Yang, Qing Fan, Danfeng Wei, Lin Wan, Xiaofeng Lu
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2017-01-01
• Series: Drug Delivery
• Subjects: photodynamic therapy; affibody; pdgfrβ; pericyte; cancer therapy
• Online Access: http://dx.doi.org/10.1080/10717544.2017.1407011

Vascular-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 death of pericytes but not of LS174T tumor cells. In mice bearing LS174T tumor grafts, ZIR700-mediated PDT damaged tumor blood vessels, thus inducing tumor destruction by intensifying tissue hypoxia. The average mass of tumor grafts administered with ZIR700-mediated PDT was approximately 20–30% of that of the control, indicating that pericyte-targeted PDT is efficient for cancer therapy. In addition, ZIR700-mediated PDT increased the tumor uptake of TNF-related apoptosis-inducing ligand (TRAIL) injected post-illumination. Consequently, combination therapy of ZIR700-mediated PDT and TRAIL showed greater tumor suppression than ZIR700-mediated PDT- or TRAIL-based monotherapy. These results demonstrated that active vascular-targeted PDT could be achieved by using ZPDGFRβ affibody-directed delivery of PS.