Photo-Fenton-like Metal-Protein Self-Assemblies as Multifunctional Tumor Theranostic Agent

Emerging Fenton-like activity of copper ions has inspired great exploration for tumor microenvironment-activated tumor therapy due to the toxic ·OH production for chemodynamic therapy and extra oxygen generation for photodynamic therapy (PDT). Still, the ·OH produced by copper ions is not satisfied even when copper ions are placed in a low pH environment (pH ≈ 5.0). To amplify its Fenton-like activity, in this work, one kind of Cu²⁺ -protein self-assemblies (C-m-ABs) loaded with photosensitizer indocyanine green (ICG) is constructed, which can catalyze H₂ O₂ generating more amounts of ·OH under light irradiation once Cu²⁺ is reduced to Cu⁺ by glutathione. Such fantastic phenomena confirms that C-m-ABs can act as a photo-Fenton-like agent. Furthermore, C-m-ABs can dramatically accelerate O₂ generation (catalase activity) to enhance the PDT of ICG. After loading with the anticancer drug doxorubicin, C-m-ABs are further self-assembled into novel nanobelts, which simultaneously exhibit superior photo-heat conversion effects, enhanced r1 relaxation (21.416 s^-1 mm^-1 ) and stimuli-responsive drug release behaviors. High cytotoxicity in vitro, effective tumor accumulation capacity observed by fluorescence/photoacoustic/magnetic resonance imaging, and enhanced chemo-/photodynamic/photothermal therapeutic performance are achieved. Based on these results, a photo-Fenton-like metal-protein self-assemblies demonstrate great potential for tumor theranostics.