• • M@P-In achieved potent antitumor efficacy in vivo with minimal systemic toxicity, as evidenced by significant tumor growth inhibition in glioblastoma-bearing mice; this addresses the critical need for therapies that overcome the BBB and immunosuppressive microenvironment, potentially extending median survival beyond the current 14-month benchmark.
• • The biomimetic coating significantly enhanced BBB penetration and tumor cell uptake, a prerequisite for effective central nervous system drug delivery; without this, even potent ICD inducers and IDO-1 inhibitors fail to reach therapeutic concentrations in the tumor parenchyma.
• • Co-delivery of paclitaxel-derived carbon dots (PCDs) and Indoximod reversed T-cell suppression and activated antitumor immune responses, as demonstrated by increased tumor-infiltrating T cells and reduced IDO-1 activity; this synergistic mechanism tackles the paucity of tumor-infiltrating T cells that limits current immunotherapies for GBM.
• • The nanocomposite leverages PCDs to induce immunogenic cell death (ICD), promoting recruitment and activation of immune cells; this ICD induction is essential for converting immunologically 'cold' GBM tumors into 'hot' tumors, thereby enhancing responsiveness to checkpoint blockade and improving overall therapeutic outcomes.