Self-assembled nano-multiple warheads: A precise targeting platform for combinatorial chemotherapy, PTT and PDT therapy against glioma.

Combination therapy tactics that incorporate numerous therapies via innovative multi-drug co-loaded nanomedicine delivery systems have shown considerable benefits in crossing the blood-brain barrier (BBB) and slowing glioma growth. However, efficiently developing multi-drug co-loaded delivery systems with high drug loading capacity, the ability to alleviate drug resistance, and minimal in vivo toxicity remains a significant problem. In this study, we created a self-assembling nanomedicine delivery system using a DIPF composite encapsulated with polydopamine and folate. The nanoparticles have an internally coated self-assembled structure that is assembled via electrostatic interactions, π-π stacking, and hydrophobic interactions between doxorubicin (DOX) and indocyanine green (ICG). This achieves high encapsulation efficiency and loading content for the co-delivery of multiple drugs. In this delivery system, the encapsulation efficiencies of DOX and ICG reached 94.08% and 94.01%, respectively, while the inherent cardiotoxicity of DOX was reduced by 64.33%. H&E staining results and anti-tumor experimental outcomes-including expression of TNF-α, Ki67, Caspase-3, and GFAP cytokines-clearly demonstrated that combined DIPF+NIR therapy significantly inhibited tumor growth and substantially extended survival. The highly efficient multi-drug co-loaded delivery system developed here demonstrates significant application potential for active targeting, controlled drug release, treatment visualization, and combined chemotherapy, photothermal (PTT), and photodynamic (PDT) therapy for brain tumors.