Photodynamic therapy (PDT) is a developing and highly promising non-invasive treatment modality for variety of cancer types, and it is still attracting great attention. Photodynamic therapy requires, light and molecular oxygen, and a photosensitizer which can yield triplet excited state upon irradiation. Excited triplet photosensitizers are able to convert molecular oxygen to cytotoxic singlet oxygen, and the latter specie is responsible for a therapeutic action. Among the several challenges in the application of PDT, penetration depth is the most pronounced one. For a satisfactory in-vitro and in-vivo PDT action, external irradiation light that is required to excite the photosensitizer should have high penetration ability in order to pass through the tissues effectively, especially in the case of deep tumors, and additionally absorption of biomolecules should be minimized. Studies have shown that red or near-IR absorbing PDT agents should be employed to get the best penetration depth and to avoid the absorption of incoming light by biomolecules. A novel red-shifted, photostable and water soluble iodo-resorufin derivative (R1) has been recently introduced as a novel PDT agent, which shows selective cytotoxicity towards MAO-A overexpressed cancer cells.1 In that study, resorufin core was decorated with iodine as a heavy atom to facilitate intersystem system crossing (ISC) for triplet excitation. Although, it has high singlet oxygen generation yield in aqueous solutions, its fluorescence quantum yield was found to be very low even after activation. In this study, iodo-resorufin core was caged with a boronate ester group (R2), which can be only cleaved by H2O2. Our results have shown that, selective cleavage of the cage group with H2O2 triggers singlet oxygen generation upon irradiation with a 595 nm LED and at the same time restores the emission of the parent core. In-vitro cytotoxicity of R2 as well as the imaging studies were completed. It was shown that R2 shows selective photocytotoxicity towards cancer cells with high H2O2 concentration and allows imaging of H2O2-postive cancer cells. This study marks the first ever example of a resorufin-based theranostic agent.

An iodinated resorufin derivative as a hydrogen peroxide activatable theranostic agent

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.