Pore size‐dependent immunogenic activity of mesoporous silica‐based adjuvants in cancer immunotherapy

Abstract Commonly used aluminum hydroxide (Alum) adjuvant provokes a strong type 2 helper T cell (Th2) response for mediating antibody production but is rather ineffective for disease prevention that requires type 1 helper T cell (Th1) response for mediating cellular immunity in human vaccination. Here, for the purpose of inducing Th1 antitumor immunity, a mesoporous silica (MS)‐based adjuvant is prepared. Three kinds of MS particles with nearly identical particle size and surface area but different pore sizes of 4, 7 and 10 nm were prepared. No serious in vitro cytotoxicity was observed for the MS particles at 5, 20, 50, and 100 μg/mL. Pathogen‐associated molecular patterns (PAMPs) were immobilized with apatite (Ap) on MS to prepare the MS‐based and PAMP‐loaded adjuvants (MS–Ap–PAMP adjuvants). Macrophage‐like cells cultured in the presence of MS–Ap–PAMP adjuvant with a MS pore size of 10 nm showed the maximum in vitro immunogenic activity. Injection of the MS–Ap–PAMP adjuvant with a MS pore size of 10 nm in combination with liquid nitrogen‐treated tumor tissue (derived from Lewis lung carcinoma cells) to C57BL/6 mice markedly inhibited the development of rechallenged tumor in vivo, while no such antitumor immunity was induced in injection of Alum mixed with PAMP in combination with liquid nitrogen‐treated tumor tissue. The MS–Ap–PAMP adjuvant contributed to the elicitation of a potent systemic Th1 antitumor immunity in vivo. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 967–974, 2014.