Abstract

Singlet oxygen generation by porphyrin-based photosensitizers is one of the main strategies used in the photodynamic therapy of cancerous lesions. In this work, we report that the complexation of tetracationic 5,10,15,20tetrakis(N-methylpiridinium-4-yl)porphyrin (TMPyP) with an acyclic cucurbituril-like container denominated M2C4 achieves quantitative generation of singlet oxygen. The complexation was studied by isothermal titration calorimetry, revealing a highly favored binding event controlled by enthalpic contributions, a stoichiometry of 1:1 and a high binding constant (K = (1.7 +/- 0.2) x 107 M-1). Photophysical studies of the complex showed bathochromic shifts in the absorption bands, increased fluorescence emission quantum yield and lengthened fluorescence lifetime. Nonetheless, fluorescence emission was minor, being intersystem crossing with the consequent generation of singlet oxygen the main deactivation pathway for the excited state. All these properties were compared with the previously reported TMPyP and cucurbit[7]uril (CB[7]) complex, which showed a superiority of the acyclic complex in terms of quantum efficiencies. Phototoxicity studies in a breast cancer cell line (MCF-7) cultured in vitro, showed that the TMPyP@M2C4 complex is unable to enter the cells even after a 24 h incubation period. However, this issue could be circumvented by encapsulating the complex into liposomes which delivered the complex to the cells efficiently. Overall, this strategy showed good potential for a highly efficient photodynamic treatment using the TMPyP@M2C4 complex in liposomal formulations.