Enhanced efficacy of PDT when combined with nitroglycerin ointment administration on xenografted retinoblastoma in mice

The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamic therapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on nude mice. 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 into 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 signalling deeper into the tumor (bystander effect).