In Vivo Documentation of Photochemical Internalization: a Novel Approach to Site Specific Cancer Therapy

Pål K. Selbo1, Gowsala Sivam2,4, Øystein Fodstad2, Kirsten Sandvig3 and Kristian Berg1
1Department of Biophysics, 2Department of Tumor Biology, 3Department of Biochemistry, Institute for Cancer Research,
The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
4Bastyr University Research Institute, Kenmore, WA, USA

ABSTRACT Photochemical internalization (PCI) is a novel technology for site-specific delivery of several types of membrane impermeable molecules to the cytosol of target cells1-5. Our technology is based on photochemical induced release of endocytosed macromolecules from endosomes and lysosomes into the cytosol (Fig. 1). The purpose of this study was to evaluate the therapeutic potential of photochemical internalization of the type I ribosomal inactivating protein gelonin in an animal model. In this report we present in vivo documentation for photochemical internalization of the type I ribosome-inactivating protein gelonin. Complete remission in 67% of the treated mice were induced.




The synergistic effect on tumor growth (Fig. 5) and cure (Tab.1) obtained by combining the ribosome-inactivating protein gelonin with photoactivation of AlPcS2a is most likely due to PCI of gelonin and not caused by other factors. Results supporting PCI as a cause of the synergistic effects are: In addition: AlPcS2a in WiDr cells in culture co-localize with fluorescence-labeled gelonin and both compounds are released from endocytic vesicles into the cytosol upon light treatment3. Photosensitizers not located in endocytic vesicles have previously been shown unsuccessful in activating the cytotoxic potential of gelonin1








CONCLUSION REFERENCES 1) Berg,K., Selbo,P.K , Prasmickaite,L., Tjelle,T.E., Kjølsrud,S., Rodal, G.H., Anholt,H., Sandvig,K., Moan,J., Gaudernack,G., Fodstad,Ø., Rodal,S.K. and Høgset,A. (1999) Photochemical internalization. A novel technology for site-specific delivery of macromolecules into cytosol. Cancer Res., 59: 1180-1183. 2) Selbo, P.K., Sivam,G., Fodstad,Ø., Sandvig.K. and Berg,K. Photochemical internalisation increases the cytotoxic effect of the immunotoxin MOC31-gelonin. (2000) Int.J.Cancer, 87: 853-859. 3) Selbo,P.K., Sandvig,K., Kirveliene,V. and Berg,K. Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization. (2000) Biochem.Biophys.Acta, 1475: 307-313. 4) Høgset,A., Prasmickaite,L., Tjelle,T.E. and Berg,K (2000) Photochemical transfection, a new technology for light-induced, site-directed gene delivery. Hum. Gene Ther., 11: 869-880. 5) (home page of the PCI-group) ACKNOWLEDGEMENTS This investigation was supported by grants from The Norwegian Cancer Society (# 96138/007), The Norwegian Radium Hospital and PhotoCure ASA. We also thank Dr. Qian Peng for helpful discussion and Fabio Apricena, Siri Juell and Øyvind Edon Olsen for technical assistance.