Coordination catalysis of metals and polydopamine enables controlled release of CO from MnCO by enhancing oxidative stress and the thermal effect

Abstract

Gas therapy based on carbon monoxide (CO) has attracted extensive attention. A key challenge in this treatment lies in the uncontrollable release of CO at the tumor site. To address this core issue, we proposed a manganese carbonyl (MnCO) delivery system with ZIF-8 as a carrier, which is encapsulated with polydopamine (PDA) to produce core–shell ZIF-8/MnCO@PDA (ZMP). ZMP formed metal–polyphenol hybrids between the core–shell interlayers to prevent uncontrolled binding of the metal with polyphenols when simultaneously added to form a normal metal–polyphenol network shell, prohibiting the aggregation of nanoparticles. The polymerization of dopamine (DA) protonated the imidazole ligands in ZIF-8/MnCO (ZM) to initiate the release of Zn ions and MnCO. Zn and MnCO coordination with PDA increases the reduction potential and decreases the oxidation potential of PDA, which is conducive to enhancing the superoxide dismutase (SOD)-like activity of PDA, thereby generating hydrogen peroxide (H₂O₂) and stimulating CO production. In addition, the coordination increases the NIR absorption of PDA, improves its photothermal capability, and facilitates the further release of CO. The oxidative stress and thermal effect cause MnCO dissociation into CO and Mn²⁺ to facilitate chemodynamic therapy (CDT). Moreover, ZMP-mediated multimodal therapy can trigger enhanced immunogenic cell death (ICD) and the stimulator of interferon genes (STING) signaling pathway.