A Supramolecular Approach for Modulated Photoprotection, Lysosomal Delivery, and Photodynamic Activity of a Photosensitizer

Abstract

Prompted by a knowledge of the photoprotective mechanism operating in photosystem supercomplexes and bacterial antenna complexes by pigment binding proteins, we have appealed to a boxlike synthetic receptor (<b>ExBox</b>·4Cl) that binds a photosensitizer, 5,15-diphenylporphyrin (<b>DPP</b>), to provide photoprotection by regulating light energy. The hydrophilic <b>ExBox</b>⁴⁺ renders <b>DPP</b> soluble in water and modulates the phototoxicity of <b>DPP</b> by trapping it in its cavity and releasing it when required. While trapping removes access to the <b>DPP</b> triplet state, a pH-dependent release of diprotonated <b>DPP</b> (<b>DPPH₂</b>²⁺) restores the triplet deactivation pathway, thereby activating its ability to generate reactive oxygen species. We have employed the <b>ExBox</b>⁴⁺-bound <b>DPP</b> complex (<b>ExBox</b>⁴⁺⊃<b>DPP</b>) for the safe delivery of <b>DPP</b> into the lysosomes of cancer cells, imaging the cells by utilizing the fluorescence of the released <b>DPPH₂</b>²⁺ and regulating photodynamic therapy to kill cancer cells with high efficiency.