Highly efficient destruction of squamous carcinoma cells of the head and neck by photochemical internalization of Ranpirnase
Nora Liebers, Tim Holland-Letz, Mona Welschof, Anders Høgset, Dirk Jäger, Michaela A. E. Arndt and Jürgen Krauss
Introduction: Photochemical Internalization is a novel drug delivery technology for cancer treatment based on the principle of Photodynamic Treatment. Using a photosensitizer that locates in endocytic vesicles membranes of tumor cells, Photochemical internalization enables cytosolic release of endocytosed antitumor agents in a site-specific manner. The purpose of the present in-vitro study was to explore whether Photochemical Internalization is able to enhance the efficacy of Ranpirnase, a cytotoxic amphibian ribonuclease, for the eradication of squamous cell carcinoma of the head and neck.
Methods: Cell viability was measured in 8 primary human cell lines of squamous cell carcinoma of the head and neck after treatment with Ranpirnase and Photochemical Internalization. For Photochemical Internalization the photosensitizer disulfonated tetraphenyl porphine was incubated with tumor cells followed by exposure to blue light (435 nm).
Results: Our study demonstrates significant enhancement of antitumor activity of Ranpirnase by Photochemical Internalization. Treatment responses were heterogeneous between the primary cancer cell lines. Combining Photochemical Internalization with Ranpirnase resulted in 4.6 to 1,940-fold increased cytotoxicity when compared with the ribonuclease alone (P < 0.05).
Conclusion: Cytotoxicity of Ranpirnase can be markedly enhanced by Photochemical Internalization in squamous cell carcinoma of the head and neck.
Keywords: Ranpirnase, Onconase®, Ribonuclease, Photochemical internalization, Photodynamic therapy, Squamous cell carcinoma of the head and neck