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

Abstract

Lu (2017) PDGFRβ-specific affibody-directed delivery of a photosensitizer, IR700, is efficient for vascular-targeted photodynamic therapy of colorectal cancer, Drug Delivery, 24:1, 1818-1830, DOI: 10.1080/10717544.2017 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. PDGFRb is abundantly expressed in the pericytes of various tumors. In this experiment, a dimeric Z PDGFRb affibody with a 0.9 nM affinity for PDGFRb was produced. The Z PDGFRb affibody showed PDGFRb-dependent pericyte binding. Intravenously injected Z PDGFRb affibody was predominantly distributed on pericytes and thus accumulated in LS174T tumor grafts. The conjugate of the Z PDGFRb affibody and IR700 dye, i.e. Z IR700 , bound to PDGFRb þ pericytes but not to PDGFRb À LS174T tumor cells. Accordingly, Z IR700 -mediated PDT in vitro induced the death of pericytes but not of LS174T tumor cells. In mice bearing LS174T tumor grafts, Z IR700 -mediated PDT damaged tumor blood vessels, thus inducing tumor destruction by intensifying tissue hypoxia. The average mass of tumor grafts administered with Z IR700 -mediated PDT was approximately 20-30% of that of the control, indicating that pericyte-targeted PDT is efficient for cancer therapy. In addition, Z IR700 -mediated PDT increased the tumor uptake of TNF-related apoptosis-inducing ligand (TRAIL) injected post-illumination. Consequently, combination therapy of Z IR700 -mediated PDT and TRAIL showed greater tumor suppression than Z IR700 -mediated PDT-or TRAIL-based monotherapy. These results demonstrated that active vascular-targeted PDT could be achieved by using Z PDGFRb affibody-directed delivery of PS. ARTICLE HISTORY

Nanoparticle drug delivery systems: an excellent carrier for tumor peptide vaccines

“…Specially, the blending of disciplines produces new research so that we should connect actively with other project like topical photodynamic therapy (PDT), which is also potential to treat cancer (Gomes et al., 2005 ). It is controllable by light with specific wavelength (Shi et al., 2017 ). And some nanostructured carriers in PDT is reported (Liu et al., 2016 ; Qidwai et al., 2016 ).…”

Stabilized tetraether lipids based particles guided prophyrins photodynamic therapy

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Vascular targeted photodynamic therapy: A review of the efforts towards molecular targeting of tumor vasculature

“…However, it is known that the walls of tumor vasculature predominantly consist of irregularly lined endothelial cells and pericytes [59]. Consequently, pericytetargeted PDT has also been explored, namely through targeting of the plateletderived growth factor receptor b (PDGFRb) [60]. PDGFRb is a tyrosine kinase receptor, crucial for the development of kidney, lung and cardiovascular system in the embryo.…”

“…To target PDGFRb, a dimeric Z PDGFRb affibody was developed [60]. Affibody molecules are non immunoglobulinderived affinity proteins based on a threehelical bundle protein domain [62].…”