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

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.

Abstract from PubMed Central (PMID 42960150, PMC13718370). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.