Macrophage membrane camouflaged manganese cross-linked phosphorus doped carbon dot for brain glioma therapy

• A macrophage membrane–coated nanoplatform (P-CDCs/Mn) penetrates the blood–brain barrier and selectively accumulates in glioma tissue through biomimetic targeting. • The acidic and oxidative tumor microenvironment triggers on-site release of active components, enabling disease-responsive imaging and therapy. • Tumor-activated manganese ions induce localized reactive oxygen species generation, achieving effective glioma suppression with minimal systemic toxicity. Glioma is an aggressive and deadly primary brain tumor of the central nervous system, characterized by poor prognosis, frequent recurrence, and low survival rates. Developing advanced nanomedicine formulations capable of crossing the blood–brain barrier (BBB) and enabling effective theranostics applications for glioma remains a significant scientific and clinical challenge. Herein, we present macrophage membrane-coated phosphorus-doped carbon dots (P-CDs) cross-linked with Mn 2+ (P-CDCs/Mn@M1) that traverse the BBB and accumulate in glioma tissue. These nanoclusters respond to the tumor-microenvironment (TME) by releasing Mn 2+ and CDs, which restore fluorescence emission and significantly enhance T1-weighted MR relaxivity, demonstrating the potential of the platform for fluorescence and MRI signal activation under TME conditions. Concurrently, Mn 2+ catalyzes Fenton-like reactions generating hydroxyl radicals and depletes glutathione, enhancing chemodynamic therapy efficacy. In orthotopic glioma models, P-CDCs/Mn@M1 demonstrated effective tumor suppression with minimal systemic toxicity. Overall, the developed nanoplatform represents a promising metal ion-driven, self-assembled CDs-based nanomedicine for with potential for imaging-assisted chemodynamic therapy in glioma.