Coordination-Regulated Terpyridine–Mn(II) Complexes for Photodynamic Therapy Guided by Multiphoton Fluorescence/Magnetic Resonance Imaging

The synergy of multiphoton fluorescence imaging (MP-FI) and magnetic resonance imaging (MRI) provides an imaging platform with high resolution and unlimited penetration depth for early disease detection. Herein, two kinds of terpyridine-Mn(II) complexes (FD-Mn-O₂NO and FD-Mn-FD) possessing seven and six coordination modes, respectively, were designed rationally for photodynamic therapy (PDT) guided by MP-FI/MRI. The complexes obtain different multiphoton fluorescence/magnetic resonance properties by adjusting the number of terpyridine ligands. Among them, FD-Mn-FD exhibits the following superiorities: (1) The optimal three-photon excitation wavelength of FD-Mn-FD falls at 1450 nm (NIR-II), which brings high sensitivity and deep tissue penetration in MP-FI. (2) FD-Mn-FD has effective longitudinal relaxation efficiency (r₁ = 2.6 m M^-1 s^-1), which can be used for T₁-weighted MRI, overcoming the problems of limited tissue penetration depth and low spatial resolution. (3) FD-Mn-FD generates endogenous ¹O₂ under irradiation by 808 nm light, thereby enhancing the PDT effect in vitro and in vivo. To the best of our knowledge, the complex FD-Mn-FD is the first complex to guide PDT through MP-FI/MRI, providing a blueprint for accurate and effective early detection and timely treatment of the complex in the early stages of cancer.