Abstract
ABSTRACT
Despite significant advances in nanovaccine development, their efficacy remains hindered by poor antigen presentation, limited antigen repertoire, and suboptimal T cell priming. Immune adjuvants such as polyinosinic‐polycytidylic acid (POLY(I:C)) exert antitumor effects by promoting dendritic cell (DC) maturation and stimulating innate immunity, but their efficacy is limited by poor antigen presenting cell (APC) uptake and weak CD8
+
T cell responses. Here, we propose a novel adjuvant strategy using nitric oxide (NO), a bioactive gaseous molecule, to upregulate MHC‐I and enhance DC cross‐presentation, thereby synergistically improving the adjuvant efficacy of POLY(I:C). We developed a nanovaccine, Im@NOnanoPL, by co‐encapsulating a preassembled complex of DOTAP, NOC‐18, and POLY(I:C) into a PLGA shell, which was further modified with DSPE‐PEG
2000
and camouflaged with immunogenic cell death (ICD)–derived tumor membranes for broad‐spectrum tumor antigen coverage. Im@NOnanoPL elicited robust and durable CD8
+
T cell responses, conferring near‐complete prophylactic protection and, in combination with αPD‐1 therapy, eradicating established tumors while inducing long‐term immune memory. Im@NOnanoPL constitutes a novel vaccine platform that integrates a gas‐based adjuvant with broad‐spectrum antigens, exhibiting strong translational potential.