Octopus-inspired polymeric nanovaccine enables high antigen loading and robust T cell activation for cancer...

Tumor vaccines hold significant promise for immunotherapy, but are limited by low antigen loading capacity, inefficient cytosolic delivery, and suboptimal T cell activation. Here, we present an octopus-inspired polymeric nanovaccine that integrates high antigen-loading capacity and effective cytosolic delivery within a single polymeric platform. The nanovaccine is constructed by encapsulating antigens with an imidazole-functionalized fluorinated polyethyleneimine and Mn²⁺ ions, forming a structure that mimics octopus tentacles and suction cups, where the PEI backbone acts as tentacle-like arms and the imidazole-Mn²⁺ units serve as suction cups. This multivalent interface enables robust antigen binding through electrostatic, coordination, and hydrophobic interactions. Beyond stabilizing the antigen payload, the amphiphilic cationic design of the polymers offers efficient cytosolic delivery of antigens into dendritic cells (DCs). Meanwhile, the intracellular release of Mn²⁺ activates the STING pathway, promoting innate immune responses. Consequently, the vaccine elicits robust antigen-specific CD8⁺ T cell responses and durable antitumor immunity in multiple tumor models. This work presents a streamlined, multifunctional strategy to overcome delivery barriers in cancer vaccines.