Manganese ion chelated nanoassemblies synergizing metalloimmunotherapy - chemodynamic for potentiating glioblastoma treatment

Glioblastoma (GBM) remains among the most aggressive brain malignancies, necessitating the development of novel therapeutic strategies. In this study, we designed a multifunctional magnetic-targeting nanoassembly (MnBPDF) by chelating Mn²⁺ with a dopamine-modified albumin coat, encapsulating a magnetic core constructed with magnetic Fe₃O₄ and doxorubicin. MnBPDF effectively induces oxidative stress and triggers immunogenic cell death (ICD), thereby releasing damage-associated molecular patterns that prime antigen-presenting cells (APCs) and subsequently activate tumor-specific cytotoxic T lymphocyte (CTL) responses. Moreover, Mn²⁺ simultaneously enhances the activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, triggering robust type I interferon production and amplifying antitumor immune responses. By boosting antigen presentation by dendritic cells (DCs) in the GBM microenvironment, this system promotes CTL infiltration and inhibits tumor progression. The synergistic effects of magnetic targeting, ICD induction, and enhanced immune activation highlight MnBPDF as a highly effective therapeutic strategy for GBM. © The Author(s) 2025.