Copper–manganese hybrid nanogel for MRI-guided combined photothermal and chemodynamic tumor theranostics

Bridging tumor diagnosis and therapy remains a major challenge, largely due to the clinical separation of imaging and treatment, compounded by the low relaxivity of conventional MRI contrast agents. To address these limitations, we developed a copper–manganese hybrid nanogel (CMNG) via the in situ incorporation of Mn²⁺ ions and CuS nanoparticles within a cross-linked polymeric network. This multifunctional design enables T₁-weighted MRI-guided photothermal–chemodynamic therapy. The nanogel matrix significantly enhances the relaxivity of paramagnetic Mn²⁺ ions (r₁ = 10.81 mM⁻¹ s⁻¹), surpassing that of clinically approved Gd-based agents. Under 808 nm laser irradiation, CMNG exhibits efficient photothermal conversion (η = 23.29%), which synergistically enhances Cu⁺/Mn²⁺-mediated Fenton-like reactions, resulting in elevated hydroxyl radical (˙OH) production for effective tumor ablation and inhibition of tumor progression. This work presents a rational materials design strategy for integrated theranostic platforms. By combining MRI-guided tracking with potent therapeutic efficacy, the CMNG system offers a promising paradigm for precision cancer theranostics.