Dual-targeting prodrug nanotheranostics for NIR-Ⅱ fluorescence imaging-guided photo-immunotherapy of glioblastoma

Glioblastoma (GBM) therapy is severely impaired by the blood-brain barrier (BBB) and invasive tumor growth in the central nervous system. To improve GBM therapy, we herein presented a dual-targeting nanotheranostic for second near-infrared (NIR-II) fluorescence imaging-guided photo-immunotherapy. Firstly, a NIR-Ⅱ fluorophore MRP bearing donor-acceptor-donor (D-A-D) backbone was synthesized. Then, the prodrug nanotheranostics were prepared by self-assembling MRP with a prodrug of JQ1 (JPC) and T7 ligand-modified PEG5k-DSPE. T7 can cross the BBB for tumor-targeted delivery of JPC and MRP. JQ1 could be restored from JPC at the tumor site for suppressing interferon gamma-inducible programmed death ligand 1 expression in the tumor cells. MRP could generate NIR-II fluorescence to navigate 808 nm laser, induce a photothermal effect to trigger in-situ antigen release at the tumor site, and ultimately elicit antitumor immunogenicity. Photo-immunotherapy with JPC and MRP dual-loaded nanoparticles remarkably inhibited GBM tumor growth in vivo. The dual-targeting nanotheranostic might represent a novel nanoplatform for precise photo-immunotherapy of GBM.