Lymph node delivery of immunogenic dendritic cell exosomes via extended-tip microneedles for cancer prevention.

Cancer prevention remains a significant challenge due to the ubiquitous presence of potentially malignant cells in the body. This study presents a novel cancer vaccine platform aimed at training the immune system to prevent the development of solid tumors. We engineered a nanostimulator (nano-IS3) comprising survivin-encoding plasmid DNA, polyethylenimine, and interferon-β-expressing nanoprotoplasts to activate dendritic cells (DCs), producing immunogenic exosomes enriched with survivin-derived antigens and costimulatory molecules (IdE@S). These IdE@S were loaded into long-tipped, high-mechanical strength dissolvable microneedles (HdMN-IdE@S) designed to penetrate the dermis for enhanced delivery to draining lymph nodes. In vitro studies demonstrated enhanced T cell activation by IdE@S compared to conventional exosomes. In vivo, the HdMN-IdE@S vaccine induced robust CD8+ T cell responses, potentially enabling continuous immune surveillance against emerging cancer cells. Importantly, this prevention strategy showed no systemic toxicity or organ damage. This approach offers a potent, safe, and patient-friendly method for cancer prevention, potentially advancing the clinical translation of tumor-associated antigen-based immunotherapies for maintaining long-term cancer-free status.