Glioma-targeted multifunctional nanoparticles to co-deliver camptothecin and curcumin for enhanced chemo-immunotherapy

Camptothecin (CPT) is a potent broad-spectrum antitumor agent with efficient therapeutic effect for various cancers. However, its application in glioma therapy has been impeded by the tumor immunosuppressive environment and blood-brain barrier (BBB)-associated drug delivery challenges. Herein, neurotransmitter analogs-modified liposomes (NTs-LIP) were prepared by doping lipidized tryptamine (Tryp) to co-deliver CPT and curcumin (CUR) for improved chemo-immunotherapy in glioma. The introduction of Tryp promotes the delivery efficiency of CPT and CUR across the BBB. CPT inhibits cell proliferation after cellular uptake of NTs-LIP, the combination of which with CUR downregulates the elevated expression of the programmed cell death 1 ligand 1 (PD-L1) caused by CPT to prevent the inactivation of T-cells and synergistically enhance chemo-immunotherapy efficacy. Furthermore, both Tryp and CUR interfere with the indoleamine 2,3-dioxygenase (IDO) pathway to reduce regulatory T cell (Treg)-mediated immunosuppression, exhibiting the potential to combine with PD-L1 inhibition for synergistic antitumor immunity. Taken together, this platform contributes towards targeted delivery and alleviation of the immunosuppressive environment in glioma therapy.