Photostable Mn(II) Complex of Curcumin for Effective Photodynamic Therapy and Precise Three-Dimensional Tumor Imaging.

Photoactive complexes of first-row transition metals with emission properties offer a dual approach to cancer treatment, enabling precise optical tumor detection and subsequent eradication using light. We report a photostable and photoactive mixed-ligand Mn(II) complex, , featuring a naturally occurring curcumin ligand and dipyridophenazine base. demonstrates significant visible and red light-triggered phototoxicity against cancer cells and precise tumor imaging capability . The complex exhibits an absorption band in the visible region, extending its tail into the red region, and shows excellent dark and photostability in solution. induces significant phototoxicity against HeLa (cervical), A549 (lung), and MCF-7 (breast) cancer cells (IC ≈ 1.0 μM), as well as 3D multicellular tumor spheroids, under low-energy visible (400-700 nm) and red-light (660 nm). This effect is mediated by cytotoxic singlet oxygen and proceeds via an apoptotic mechanism. Importantly, displays significantly lower toxicity toward normal HPL1D lung and HEK-293 kidney cells under similar conditions. Cellular uptake studies reveal selective accumulation of in A549 cancer cells, with mitochondrial localization, and negligible accumulation in BEAS-2B normal lung cells. Furthermore, 3D optical tumor imaging demonstrated 's selective tumor accumulation in a 4T1 breast tumor-bearing mouse model. efficacy studies using a 4T1 tumor-bearing orthotopic mouse model show that significantly reduces tumor volume and weight in a dose-dependent manner under low-energy blue laser (450 nm) irradiation, highlighting its potential as an effective photodynamic therapy (PDT) agent. Toxicological studies confirm that does not induce abnormal biochemical or hematological parameters in healthy mice. To our knowledge, this is the first report of a Mn(II) complex with curcumin and the first example of a metal complex with curcumin for combined PDT and noninvasive 3D optical tumor imaging, paving the way for nonmacrocyclic Mn-based cancer phototheranostics.