A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Abstract

Cancer vaccine gains great attention with the advances in tumor immunology and nanotechnology, but its long-term efficacy is restricted by the unsustainable immune activity after vaccination. Here, we demonstrate the vaccine efficacy is negatively correlated with the tumor burden. To maximum the vaccineinduced immunity and prolong the time-effectiveness, we design a priming−boosting vaccination strategy by combining with radiofrequency ablation (RFA), and construct a bisphosphonate nanovaccine (BNV) system. BNV system consists of nanoparticulated bisphosphonates with dual electric potentials (BNV(+&−)), where bisphosphonates act as the immune adjuvant by blocking mevalonate metabolism. BNV(+&−) exhibits the spatial and temporal heterogeneity in lymphatic delivery and immune activity. As the independent components of BNV(+&−), BNV(−) is drained to the lymph nodes, and BNV(+) is retained at the injection site. The alternately induced immune responses extend the time-effectiveness of antitumor immunity and suppress the recurrence and metastasis of colorectal cancer liver metastases after RFA. As a result, this trinity system integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal immune effect provides an orientation for the sustainable regulation and precise delivery of cancer vaccines.