Cavity-Size-Adjustable Macrocycles as a Novel Vaccine Adjuvant for Tumor Immunotherapy

In this study, we constructed a macrocycle-based vaccine system driving antigen accumulation in lymph nodes. The capabilities of antigen delivery and immune activation as vaccine adjuvants are based on three positively charged water-soluble biphen[3]arenes (WP 3s: WTP3, WQP3, and WPP3) with different cavity sizes were synchronously investigated. Compared to the OVA group, WTP3, WQP3, and WPP3 exhibited a significant increase in the IgG antibody titer by ∼ 2.3 × 10²-, 2.7 × 10³-, and 7.6 × 10³-fold, respectively. Therefore, we are convinced that biphen[3]arenes with larger cavity sizes not only demonstrate enhanced protein loading and binding capacity in vitro, but also manifest prolonged antigen retention time and heightened immune activation ability in vivo. To the best of our knowledge, this study represents the initial exploration of the impact of macrocyclic cavity sizes on the efficiency of antigen delivery as well as its potential influence on immune response capabilities.