Photodynamic therapy (PDT) utilizing an organic dye (photosensitizer) capable of killing cancer cells in the body upon light irradiation is one of the promising non-invasive treatment modalities for many cancers. A known drawback of PDT is a side-effect caused by existing photosensitizers to organs due to insufficient specificity and accidental light exposure of a patient during the delivery of the photosensitizer in the bloodstream. To overcome this issue, we developed a novel antibody guided, activatable photosensitizing system, Ab-mI2XCy-Ac, where the trastuzumab (Ab) is linked to the non-active (not phototoxic and not fluorescent) dye, mI2XCy-Ac, that contains the hydroxyl group protected by acetyl (Ac). This targeting, non-photo-active conjugate was shown to be safely (without detectable side-effects) delivered to the targeted tumor, where it is activated by the esterase-mediated acetyl group cleavage and effectively treats the tumor upon NIR light irradiation. It was demonstrated in the Her2 positive BT-474 tumor mouse model that the treatment efficacy of the activatable photosensitizing system is about the same as for the permanently active photosensitizer, Ab-mI2XCy, while the side-effects are noticeably reduced. In addition, this activatable system enables fluorescence monitoring of the photosensitizer activation events.
Keywords: Activatable photosensitizer; Antibody carrier; Fluorescence monitoring; Photodynamic therapy; Reduced side-effects.
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