Resiquimod-Induced Nanovaccine (RINV) for Personalized Cancer Immunotherapy

Cancer nanovaccines have emerged as a promising modality for cancer immunotherapy due to their capability of eliciting robust tumor-specific immune responses. However, structural complexity and insufficient spatiotemporal coordination of immune activation pose substantial challenges for optimizing the therapeutic potential of nanovaccines. Herein, a resiquimod-induced nanovaccine (RINV) is devised for personalized cancer immunotherapy. Toll-like receptor (TLR) 7/8 agonist resiquimod (R848) was covalently conjugated to fifth-generation polyamidoamine (G5-PAMAM) dendrimer through a disulfide linker to obtain the vaccine carrier G5-R848. In this design, R848 not only fulfills its biological role as a vaccine adjuvant but facilitates uniform nanovaccine formation with the model protein antigen ovalbumin (OVA) due to its distinctive chemical structure. Redox-triggered intracellular R848 release further promotes cytosolic delivery of antigen and subsequent antigen cross-presentation. In vivo studies demonstrated that the nanovaccine induces remarkable prophylactic and therapeutic effects in the B16F10-OVA melanoma model. Moreover, G5-R848 forms personalized nanovaccines by complexing with cell lysates from resected B16F10 and 4T1 tumor tissues, effectively inhibiting postoperative tumor recurrence and metastasis.