An Aggregation-Induced Emission Molecule-Assembled Nanovaccine with Self-Adjuvanted Function for Cancer Immunotherapy

Cancer nanovaccine is a promising therapeutic strategy; however, the complicated composition and ambiguous structure of cancer nanovaccines hinder their clinical application. Thus, developing minimalist nanovaccine with simple structural molecule and potent immunostimulatory function is with great value. Herein, an organic small molecule with well-defined molecular structure and strong aggregation-induced emission (AIE) activity is synthesized. This molecule can self-assemble into nanoparticle (NM-7) acting as not only adjuvant but also carrier to capture model antigen ovalbumin to form nanovaccine, which can effectively deliver and chronically release antigens and induce effective antigen cross-presentation in draining lymph nodes. Additionally, the photophysical property of AIE molecule facilitates the determination of in vivo tissue distribution of NM-7. Notably, NM-7/ovalbumin (OVA) nanovaccine induces robust tumor-specific CD8(+) T-cell responses with greatly reduced cell exhaustion. Accordingly, NM-7/OVA nanovaccine shows potent efficacy in both prevention and therapeutic tumor models, and produces an impressive synergistic therapeutic effect when combined with immune checkpoint blockade (ICB) therapy. Therefore, AIE nanomaterial NM-7 with simple synthesis, well-defined molecular structure and self-adjuvanted function provides a new reference and general strategy for cancer vaccine development.