(1) Journal Source:
Advanced Functional Materials (2026)
(2) Title:
Manganese Nanoparticles Coupled with Adjacent Single-Atom Nanozymes for Concerted Synergistic Amplification of the cGAS-STING Pathway and Glioblastoma Immunotherapy
(3) Research Idea:
In this work, we designed a manganese nanoparticle/adjacent single-atom nanozyme complex (MnAC/SA-D@M) loaded with the STING agonist diABZI and camouflaged with homologous glioma cell membranes. Through electronic coupling between manganese clusters and adjacent single-atom sites, this nanosystem optimizes the local charge distribution and markedly boosts peroxidase-like catalytic activity. Within the tumor microenvironment, such catalysis triggers massive reactive oxygen species (ROS) generation and glutathione depletion, which initiates robust lipid peroxidation and ferroptosis. Meanwhile, catalysis-induced oxidative stress elicits immunogenic cell death (ICD) and mitochondrial damage, accompanied by mitochondrial DNA release. The released mitochondrial DNA works synergistically with Mn²⁺ generated from system degradation and the loaded diABZI to continuously activate the cGAS-STING immune signaling pathway, facilitate dendritic cell maturation and macrophage polarization toward the M1 phenotype. This reverses the immunosuppressive microenvironment of glioblastoma and achieves potent inhibition of orthotopic tumors and postoperative recurrence.
(4) Material Development:
• (1) Material: MnAC/SA-D@M composite nanozyme system. Using ZIF-8 as the template, nitrogen-doped porous carbon supports (MnAC/SA) containing manganese atomic clusters (Mn ACs) and manganese single atoms (Mn SAs) are fabricated via vapor diffusion deposition and high-temperature pyrolysis. The STING agonist diABZI is subsequently loaded through hydrophobic interactions, followed by coating the surface with homologous glioma cell membranes.
• (2) Functions: Capable of blood-brain barrier penetration and homologous tumor targeting; enhances peroxidase-like activity via electronic coupling between atomic clusters and single atoms to achieve tumor-specific hydroxyl radical production and glutathione consumption; induces ferroptosis and immunogenic cell death in tumor cells; and leverages degradation-derived Mn²⁺ together with exogenous agonists to sustainably amplify immune activation signals.
(5) Innovations:
1. Innovative Catalyst Structure: A strategy employing electronic coupling between manganese atomic clusters and neighboring manganese single-atom sites is proposed. By tuning d-electron density and charge distribution, it overcomes the limitation of insufficient adsorption affinity toward reaction intermediates in conventional single-atom nanozymes, achieving a leap in catalytic activity at the atomic level.
2. Multi-pathway Cascade Immune Activation: Ferroptosis and immunogenic cell death induced by catalytically produced ROS are deeply integrated with the cGAS-STING pathway activated by mitochondrial DNA release and the effect of exogenous STING agonists, constructing a therapeutic network with multi-level immune signal amplification.
3. Precision Targeted Delivery: The ingenious camouflage with homologous glioma cell membranes not only endows nanozymes with the active capacity to cross the blood-brain barrier but also enables precise recognition of glioblastoma.


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