Memantine biotin conjugate with intra tumoral cell displacing ability for cucurbit[8]uril-based switchable photosensitizer

Abstract

Switchable supramolecular photosensitizers have the potential to be more potent and decrease common side effects of photodynamic therapy such as patient's sensitivity to ambient light. Combining this supramolecular strategy with a cancer-targeting strategy would also improve selectivity towards tumoral cells. In this work, we take advantage of the strong binding ability of cucurbit[8]uril towards cationic photosensitizer methylene blue. Encapsulation of two molecules of methylene blue inside the cavity of cucurbit[8]uril leads to strong quenching of its photoactivity, particularly the generation of singlet oxygen. In order to release selectively the photosensitizer, we synthesized a new memantine-biotin conjugate that is able to cross a liposomal bilayer as a model for a biological membrane and bind to cucurbit[8]uril releasing the photosensitizer. This phenomenon leads to a sizable boost in singlet oxygen generation. In vitro phototoxicity studies in tumoral cells show a significant difference in cell killing after the addition of the memantine-biotin displacing agent. These studies have important potential for more selective photodynamic therapy of cancer.