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

In\nthis study, we constructed a macrocycle-based vaccine system\ndriving antigen accumulation in lymph nodes. The capabilities of antigen\ndelivery and immune activation as vaccine adjuvants are based on three\npositively charged water-soluble biphen[3]arenes (WP 3s: WTP3, WQP3,\nand WPP3) with different cavity sizes were synchronously investigated.\nCompared to the OVA group, WTP3, WQP3, and WPP3 exhibited a significant\nincrease in the IgG antibody titer by ∼ 2.3 × 10<sup>2</sup>-, 2.7 × 10<sup>3</sup>-, and 7.6 × 10<sup>3</sup>-fold,\nrespectively. Therefore, we are convinced that biphen[3]arenes with\nlarger cavity sizes not only demonstrate enhanced protein loading\nand binding capacity in vitro, but also manifest prolonged antigen\nretention time and heightened immune activation ability in vivo. To\nthe best of our knowledge, this study represents the initial exploration\nof the impact of macrocyclic cavity sizes on the efficiency of antigen\ndelivery as well as its potential influence on immune response capabilities.