Dual targeting of folate receptor-expressing glioma tumor-associated macrophages and epithelial cells in the brain using a carbon nanosphere–cationic folate nanoconjugate

Abstract

FRs. A doxorubicin-associated FR-targeting formulation (CFD), in an orthotopic glioma model and in a glioma subcutaneous model, induced the maximum anticancer effect with enhanced average mice survivability twice that of untreated mice and without any systemic liver toxicity. Additionally, we observed a significant decrease of TAM-released pro-aggressive factors, TGF-β, STAT3, invasion and migration related sICAM-1, and other cytokines indicating anti-TAM activity of the CFD. Taken together, we principally devised, to the best of our knowledge, the first FR-targeting nano-delivery system for targeting brain-associated TAMs and tumor cells as an efficient glioma therapeutic.