An aluminum adjuvant-integrated nano-MOF as antigen delivery system to induce strong humoral and cellular immune responses

Abstract

Metal-organic frameworks (MOFs) have high surface area, tunable pore size, and high loading capacity, making them promising for drug delivery. However, their synthesis requires organic solvents, high temperature and high pressure that are incompatible with biomacromolecules. Zeolitic imidazole frameworks (ZIF-8) which forms through coordination between zinc ions and 2-methylimidazole (MeIM) have emerged as an advanced functional material for drug delivery due to its unique features such as high loading and pH-sensitive degradation. In this study, we took advantage of a natural biomineralization process to create aluminum-containing nanoZIF-8 particles for antigen delivery. Without organic solvents or stabilizing agent, nanoparticles (ZANPs) were synthesized by a mild and facile method with aluminum, model antigen ovalbumin (OVA) and ZIF-8 integrated. A high antigen loading capacity (%) of 30.6% and a pH dependent antigen release were achieved. A Toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides (CpG) was adsorbed on the surface of ZANPs (hereafter CpG/ZANPs) to boost the immune response. After subcutaneous injection in vivo, CpG/ZANPs targeted lymph nodes (LNs), where their cargo was efficiently internalized by LN-resident antigen-presenting cells (APCs). ZANPs decomposition in lysosomes released antigen into the cytoplasm and enhanced cross-presentation. Moreover, CpG/ZANPs induced strong antigen-specific humoral and cytotoxic T lymphocyte responses that significantly inhibited the growth of EG7-OVA tumors while showing minimal cytotoxicity. We demonstrate that ZANPs may be a safe and effective vehicle for the development of cancer vaccines.