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

Abstract

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