Nanoengineering of Vaccine Nanoparticles via Templating of Metal–Organic Frameworks for Tumor Immunotherapy

We present a facile strategy to fabricate nanovaccines through a metal–organic framework-templated method. The nanovaccines, named IMDQ@OVA-TA, were obtained through the interfacial assembly of model antigen ovalbumin (OVA) and tannic acid (TA) on imidazoquinoline (IMDQ)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs). The coordination of Zn²⁺-imidazole, Zn²⁺-TA, and the molecular coassembly of TA with proteins resulted in the formation of stable nanovaccines under physiological conditions. The pH responsiveness granted to the nanovaccines by coordination bonds promotes IMDQ release at low pH values, antigen lysosomal escape, and cross-presentation. In C57BL/6 mice models, nanovaccines demonstrated long-term accumulation at the injection site, sustainable transportation to lymph nodes, and good therapeutic effects against E.G7-OVA lymphoma. Mechanism analysis revealed that the nanovaccines induced both innate and adaptive tumor-specific immune activation. Overall, our work presents a simple and general strategy for the fabrication of protein-polyphenol nanocapsules with toll-like receptor (TLR) 7/8 agonists for cancer immunotherapy.