A Cocrystal Strategy for Harnessing UV-Responsive Endogenous Photosensitizer in Visible Light Photodynamic Therapy

Photosensitizer plays a pivotal role in photodynamic therapy (PDT). Nonetheless, designing a photosensitizer activated by visible light from small molecules remains a significant challenge. Here, a supramolecular self-assembly donor-acceptor cocrystal is proposed as a feasible strategy to enhance the PDT of the photosensitizer. To demonstrate this concept, Vitamin K₃(VK3), a UV-responsive endogenous molecule, was selected as the acceptor, paired with tetrathiafulvalene (TTF) as the donor. TTF-VK3, as a benchmark cocrystal, were synthesized, successfully validating the capability of cocrystal engineering to extend light-responsive wavelengths of a photosensitizer. TTF-VK3 cocrystals exhibited broadened absorption achieved through ground-state charge-transfer between the donor and acceptor. Ultrafast transient absorption reveals that the charge-transfer interaction substantially diminishes Δ<i>E</i>_ST of S₁→T₁, giving rise to a charge-transfer triplet excited state upon excitation. This endows the cocrystals with an exceptional singlet oxygen (¹O₂) generation capability under visible light irradiation. The developed cocrystal photosensitizer exhibits extraordinary characteristics, including easy-to-synthesize, easy-to-tune excited-state, no chemical modification, visible light excitation, and efficient ¹O₂ generation. These exceptional properties are remarkably preserved even in nanocrystalline cocrystal, making them particularly suitable for outstanding antibacterial efficacy, along with the ability to induce phototriggered cell death of 4T1 cancer cells after visible-light exposure. This finding establishes an effective strategy for transforming UV-responsive endogenous molecules into visible-light-activatable photosensitizer.