Supramolecular photodynamic agents for simultaneous oxidation of NADH and generation of superoxide radical

Abstract

Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare Type-I PSs is of great importance, but remains a challenge. Here, we report a supramolecular strategy for the preparation of Type-I photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors to the existing Type-II PSs. As a proof-of-concept, three electron acceptors were designed and co-assembled with a classical PS to produce quadruple hydrogen-bonded supramolecular photodynamic agents. The photo-induced electron transfer from the PS to the adjacent electron acceptor occurs efficiently, leading to the generation of a strong oxidizing PS^+• and an anionic radical of the acceptor, which further transfers an electron to oxygen to form O₂^−•. In addition, these photodynamic agents induce direct photocatalytic oxidation of NADH with a turnover frequency as high as 53.7 min⁻¹, which offers an oxygen-independent mechanism to damage tumors.

Tumour hypoxia is a major issue for conventional photodynamic therapies, Here, the authors report on the supramolecular assembly of electron acceptors with photosensitizers which have improved reactive oxygen species production and are able to directly oxidise NHDH and demonstrate application against hypoxic tumours.