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

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
(ExBox·4Cl) that binds a photosensitizer, 5,15-diphenylporphyrin
(DPP), to provide photoprotection by regulating light
energy. The hydrophilic ExBox4+ renders DPP soluble in water and modulates the phototoxicity of DPP by trapping it in its cavity and releasing it when required.
While trapping removes access to the DPP triplet state,
a pH-dependent release of diprotonated DPP (DPPH22+) restores the triplet deactivation pathway,
thereby activating its ability to generate reactive oxygen species.
We have employed the ExBox4+-bound DPP complex (ExBox4+⊃DPP) for the safe delivery of DPP into the lysosomes of
cancer cells, imaging the cells by utilizing the fluorescence of the
released DPPH22+ and regulating
photodynamic therapy to kill cancer cells with high efficiency.