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

Abstract

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-FeCl 3 , TD-Fe-TD) with four-photon absorption properties were designed and synthesized. The four-photon absorption cross sections of TD-FeCl 3 reached 6.87 × 10–74cm8·s3·photon–3. Due to its strong near-infrared absorption, TD-FeCl 3 has excellent photoacoustic imaging (PAI) capability for accurate PA imaging. TD-FeCl 3 has an efficient longitudinal electron relaxation rate (r 1 = 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-FeCl 3 , 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.

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

“…Disturbing the complex homeostasis of the TME can further result in effective cancer therapy by novel cell death modalities (e.g., ferroptosis, pyroptosis, and immunogenic cell death) [ 7 , 8 , 9 ], and the resensitization of cells to conventional therapies [ 2 , 9 , 10 ]. Molecular complexes of Pt [ 11 ], Au [ 12 ], Fe [ 13 ], Os [ 14 ], Re [ 15 ], Ru [ 16 ], and Ir [ 17 ] have been reported to induce ferroptosis; their molecular structures are shown in Scheme 1 . Nevertheless, most of the current formulations are far from satisfactory for practical use due to their formidable structural complexity, high cost, and low cellular uptake that subsequently leads to low anticancer efficacy.…”