A Supramolecular Nanoformulation with Adaptive Photothermal/Photodynamic Transformation for Preventing Dental Caries

In the context of an increasingly escalating antibiotics crisis, phototherapy has emerged as a promising therapeutic approach due to its inherent advantages, including high selectivity, noninvasiveness, and low drug resistance. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two complementary and promising phototherapies albeit with inherent limitations, noted as the challenges in achieving precise heat confinement and the associated risk of off-target damage for PTT, while the constraints due to the hypoxic microenvironment are prevalent in biofilms faced by PDT. Herein, we have designed a supramolecular nanoformulation that leverages the complexation-induced quenching of guanidinium-modified calix[5]arene grafted with fluorocarbon chains (GC5AF₅), the efficient recognition of adenosine triphosphate (ATP), and the oxygen-carrying capacity of the fluorocarbon chain. This intelligent nanoformulation enables the adaptive enhancement of both photothermal therapy (PTT) and photodynamic therapy (PDT), allowing for on-demand switching between the two modalities. Our nanoformulation utilizes ATP released by dead bacteria to accelerate the elimination of biofilms, rendering bacteria unable to resist while minimizing harm to healthy tissues. This research highlights the particular recognition and assembly capabilities of macrocycles, offering a promising strategy for creating potent, combined antibiofilm therapies.