Vascular endothelial cells as targets for photochemical internalization (PCI)

Authors

  • Marie Vikdal,

    Corresponding author
    • Department of Radiation Biology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    Search for more papers by this author
  • Anette Weyergang,

    1. Department of Radiation Biology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    Search for more papers by this author
  • Pål Kristian Selbo,

    1. Department of Radiation Biology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    2. Cancer Stem Cell Innovation Center (SFI-CAST), Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    Search for more papers by this author
  • Kristian Berg

    1. Department of Radiation Biology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    Search for more papers by this author

Corresponding author email: marie.vikdal@rr-research.no (Marie Vikdal)

Abstract

Cancer treatment can be exerted by targeting both cancer cells and the vasculature supplying solid tumors. Photochemical internalization (PCI) is a modality for cytosolic drug delivery, but recent data on contrast-enhanced MRI have indicated that the method also reduces blood perfusion in HT1080 fibrosarcoma xenografts. The present report aims to investigate if PCI may exert direct cytotoxic effects on endothelial cells. PCI of saporin was performed on endothelial human umbilical vein endothelial cell (HUVEC) and fibrosarcoma cells (HT1080) using two PCI-relevant photosensitizers, TPPS2a and AlPcS2a. A 22- and 13-fold higher photosensitizer uptake was detected in the endothelial cells compared with the HT1080 cells for AlPcS2a and TPPS2a, respectively. PCI of saporin was, however, found more effective in HT1080 cells. For HT1080 cells, PCI with saporin increased cell killing 1.9-fold over photodynamic therapy alone, but under the same conditions, only increased HUVEC cell killing by 1.6- and 1.3-fold with AlPcS2a and TPPS2a, respectively. Saporin uptake was higher in HUVECs than in the HT1080 cells, hence did not reflect the cell line differences in PCI efficacy. This is the first report on PCI-mediated kill of endothelial cells and lays the foundation for further preclinical evaluation of the PCI technology as an antivascular strategy to ablate tumors.

Ancillary