A Biomimetic Nanocomposite Co-delivering Carbon Dots and Indoximod for Synergistic Immunochemotherapy of Glioblastoma
Glioblastoma (GBM) remains the most lethal primary brain tumor, with the blood-brain barrier (BBB) severely restricting effective treatment options. Immunotherapy has achieved remarkable success in cancers such as lung cancer and melanoma, yet its efficacy in GBM is constrained by the immunosuppressive tumor microenvironment and a paucity of tumor-infiltrating T cells. This study developed a biomimetic nanocomposite for the co-delivery of an immunogenic cell death (ICD) inducer and an indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor to overcome these challenges. Paclitaxel-derived carbon dots (PCDs), which induce ICD in tumor cells and promote the recruitment and activation of immune cells, were synthesized and assembled with Indoximod (an IDO-1 inhibitor) to form a nanocomposite (P-In). A biomimetic coating was subsequently applied to create M@P-In. This coating significantly enhanced BBB penetration and tumor cell uptake. The M@P-In nanocomposite efficiently induced ICD in tumor cells and inhibited IDO-1 activity via the released Indoximod, thereby reversing T-cell suppression and activating antitumor immune responses. Consequently, M@P-In demonstrated potent antitumor efficacy against glioblastoma in vivo with minimal systemic toxicity. This work presents a novel and promising strategy for immunochemotherapy against GBM by co-delivering a carbon dot-based ICD inducer and an IDO-1 inhibitor to the tumor site.