A near-infrared/tumor microenvironment dual-responsive cobalt-based material for photothermal/photodynamic/DNA-damaging chemotherapy synergistic therapy and anti-inflammation

The co-ordination properties of biomolecules with metal ions can lead to changes in their structures and functions. This work discloses that cobalt ions (Co 2+ ) can induce structural changes in DNA by coordinating with guanine and inactivate copper/zinc superoxide dismutase (Cu/Zn-SOD) by changing the secondary structure. The Co 2+ at high concentrations can suppress cell growth and induce apoptosis. Herein, we fabricate a light and tumor microenvironment (TME) dual-responsive polydopamine-coated cobalt boride (CoB@PDA) as a Co 2+ -carrying material, NIR-driven photothermal/photodynamic agent, catalase-like nano-enzyme, reactive oxygen species (ROS) moderator, and hydrogen (H 2 ) supplier. CoB@PDA with catalase-like properties can convert the H 2 O 2 at tumor site into O 2 , ·O 2 − and 1 O 2 , thus inducing oxidative stress and alleviating tumor hypoxia. Under 808 nm irradiation, CoB@PDA can induce a hyperthermia by photothermal effect and trigger photosensitization of O 2 to toxic 1 O 2 , thus achieving the photothermal therapy (PTT) and photodynamic therapy (PDT) actions. Meanwhile, decomposition of CoB@PDA in the acidic TME releases Co 2+ to inhibit the growth of residual tumor cells post phototherapy and H 2 to suppress the inflammatory response induced by phototherapy. The complete ablation of solid tumors with no side effects and recurrence indicates that CoB@PDA is promising for cancer therapy, and thus it provides valuable insights for the development of multifunctional antineoplastic agents.