Biodegradable Charge‐Transfer Complexes for Glutathione Depletion Induced Ferroptosis and NIR‐II Photoacoustic Imaging Guided Cancer Photothermal Therapy

Abstract Suffering from the laborious synthesis and undesirable tumor microenvironment response, the exploitation of novel NIR‐II absorbing organic photothermal agents is of importance to promote phototherapeutic efficacy. Herein, two kinds of charge‐transfer complex nanoparticles (TMB‐F4TCNQ and TMB‐TCNQ) are prepared by supramolecular assembly. Because of the larger energy gap between donor and acceptor, TMB‐F4TCNQ presents higher charge‐transfer degree (72 %) than that of TMB‐TCNQ (48 %) in nanoaggregates. Therefore, TMB‐F4TCNQ exhibits stronger NIR‐II absorption ability with a mass extinction coefficient of 15.4 Lg −1 cm −1 at 1300 nm and excellent photothermal effect. Impressively, the specific cysteine response can make the TMB‐F4TCNQ effectively inhibit the intracellular biosynthesis of GSH, leading to redox dsyhomeostasis and ROS‐mediated ferroptosis. TMB‐F4TCNQ can serve as a contrast agent for NIR‐II photoacoustic imaging to guide precise and efficient photothermal therapy in vivo.