Abstract

PDT uses a non-mutagen photosensitizing agent (PS: glycoconjugated porphyrin derivative) activated by red light exposure. Absorption of light initiates photochemical reactions leading to the generation of cytotoxic photoproducts (ROSs: oxygen reactive species) responsible for the therapeutic effects [1]. We propose to increase the PDT efficiency (on our least responsive retinoblastoma line to treatment) with a better PS delivery in the tumor generated by NG which is known to dilate vessels and enhance the permeability and retention of macromolecules in solid tumors [2].

Methods: In vivo follow-up of the therapeutic effects was performed by sodium MRI which directly monitors variations of sodium concentrations in a non-invasive way and can be used to follow up the tumor response to therapy [3]. NG ointment was applied one hour before PDT. The PDT protocol implied a double tumor targeting, cellular and vascular. A first PS dose was injected followed by a second one, separated by a 3 h interval. The time-lapse allowed the PS molecules to penetrate tumor cells. Ten minutes after the second dose, the PS was red light activated.

Results: The PDT efficacy (increase of necrosis, decrease of the tumor volume) was enhanced by applying NG ointment on the skin of tumor-bearing animals.

Conclusion: NG increases the PDT efficacy by enhancing the intratumor concentration of PS inducing a more significant production of ROSs on the illuminated region increasing thus the propagation of cellular death signaling deeper into the tumor (bystander effect).