Multifunctional biliverdin-based MnO₂ nanozyme alleviates oxidative stress and immune rejection in islet graft...

Pancreatic islet transplantation is currently the only minimally invasive treatment capable of restoring endogenous insulin production and achieving long-term glycemic control in patients with type 1 diabetes. However, early graft loss remains a major limitation due to the combined impact of hypoxic stress and immune rejection at the transplantation site. In this study, we developed a biliverdin-based manganese dioxide (BV-MnO₂) nanozyme that mimics catalase activity to address these challenges. The BV-MnO₂ nanoparticles decompose excessive hydrogen peroxide (H₂O₂) into molecular oxygen, thereby alleviating the local hypoxic microenvironment and reducing oxidative stress. Furthermore, the inclusion of biliverdin imparts anti-inflammatory and immunoregulatory properties, effectively suppressing T cell activation and promoting immune tolerance. In vitro and in vivo experiments demonstrated that BV-MnO₂ enhances islet viability, preserves insulin secretion, inhibits inflammatory infiltration, and significantly prolongs graft survival, maintaining normoglycemia for over 35 days post-transplantation. Additionally, the release of Mn²⁺ enables magnetic resonance imaging (MRI) monitoring of graft viability, offering theranostic potential. These findings suggest that BV-MnO₂ represents a promising nanomedicine platform that integrates antioxidative protection, immune modulation, and real-time imaging, providing a multifaceted strategy to improve the efficacy and monitoring of clinical islet transplantation.