Four-Photon Absorption Iron Complex for Magnetic Resonance/Photoacoustic Dual-Model Imaging and an Enhanced Ferroptosis Process

Four-photon absorption (4PA) multimodal therapeutic agent applied to tumor ferroptosis process tracking is rarely reported. In this paper, two functionalized terpyridine iron complexes (TD-FeCl₃, TD-Fe-TD) with four-photon absorption properties were designed and synthesized. The four-photon absorption cross sections of TD-FeCl₃ reached 6.87 × 10^–74cm⁸·s³·photon^–3. Due to its strong near-infrared absorption, TD-FeCl₃ has excellent photoacoustic imaging (PAI) capability for accurate PA imaging. TD-FeCl₃ has an efficient longitudinal electron relaxation rate (r₁ = 2.26 mM^–1 s^–1) and high spatial resolution, which can be applied as T₁-weighted magnetic resonance imaging (MRI) contrast agent for tumor imaging in vivo. In addition, Fe³⁺ as a natural ferroptosis tracer, TD-FeCl₃, is able to deplete glutathione (GSH) effectively, which can further enhance the ferroptosis process. We found that the series of cheap transition metal complexes has four-photon absorption activity and can be used as multimodal (MRI/PAI) diagnostic agents for tumor tracing processes.