Enhanced NIR-triggered photo-to-chemo conversion based on plasmonic heterojunction nanozyme for tetra-hybrid antineoplastic therapy

Photo-activated thermal and dynamic therapy is confirmed as a secure modality for tumor ablation due to its non-invasiveness. However, photothermal and photodynamic therapy in phototherapy often do not have uniform wavelengths due to the different materials used, and the infrared light used in photothermal therapy is considered difficult to excite photosensitizers such as porphyrins. Herein, a plasmonic heterojunction nanozyme with a core–shell structure and bimetal nodes (Cu & Mn) was designed. The excitation wavelength of photo-to-chemo conversion in the photodynamic effect of porphyrin is adjusted by using the surface plasmon resonance and heterojunction to achieve the result of simultaneous excitation of photothermal and photodynamic effects by near-infrared light. Results showed that the kinetic size of Bi@MOF was 110 nm, with heterojunction features, which were characterized by reduced impedance, enhanced photocurrent response, and staggered band crossing. Physical and chemical characterization illustrated that Bi@MOF heterojunction could change the wavelength required for the photodynamic effect of porphyrin-based metal–organic framework from 650 nm to 808 nm by surface plasmon resonance-induced high-energy excitons generation as well as shortened Stokes shifts. At the same time, the bimetal in the nanozyme can generate the reactive oxygen species storm through the bimetal-enhanced Russell mechanism and the tumor microenvironment-responsive Fenton reaction and photodynamic effect. Cell and animal tests illustrated that the glutathione oxidase-like activity of nanozymes can trigger ferroptosis in cancer cells, further disrupting intracellular redox homeostasis. Finally, a hybrid nanotherapy system was created, which realizes the integration of four therapies, including photothermal, photodynamic, chemodynamic, and ferroptosis.