Exosome-Coated Dendrimer Nanogels as a Therapeutic Vaccine for CT Imaging-Guided Chemoimmunotherapy of Pancreatic Cancer

High Resolution Image Download MS PowerPoint Slide Development of new medicines that can treat pancreatic cancer with a sustained immune memory effect remains to be a challenging task. Herein, we report a tumor microenvironment-responsive dendrimer nanogel (DNG)-based therapeutic vaccine co-loaded with toyocamycin (Toy) and gold nanoparticles (Au NPs) and the surface camouflaged with Cytosine-phosphate-Guanine (CpG)-functionalized exosomes derived from pancreatic cancer cells (termed as Au@DNG@C-Exo) for computed tomography (CT) imaging and chemoimmunotherapy of pancreatic cancer. The created Au@DNG@C-Exo through a reverse-phase microemulsion method displays a size of 105.6 nm with a narrow distribution, desired colloidal stability, and stimuli-responsive Toy release profile. We show that Au@DNG@C-Exo enables Exo-mediated homologous targeting chemotherapy of cancer cells to induce efficient immunogenic cell death (ICD), which synergizes with the CpG adjuvant/Exo antigen presentation to maturate dendritic cells (DCs), thereby initiating a potent antigen-specific anticancer immune response. Concurrently, the incorporated Au NPs repolarize tumor-associated macrophages from the M2 to the antitumor M1 phenotype and serve as contrast agents for CT imaging of tumors in vivo . The Au@DNG@C-Exo-mediated chemoimmunotherapy maximally suppresses the growth of Panc-02 tumors in a mouse model and elicits a robust systemic anti-tumor immune response. Meanwhile, Au@DNG@C-Exo also effectively prevents tumor occurrence after immunization. The developed DNG-based therapeutic nanovaccine that is able to modulate triple cell types, including cancer cells, DCs, and macrophages, presents a promising theranostic strategy to tackle pancreatic cancer.