Atomic force microscopy-based exploration of layered double hydroxide nanoparticles adjuvant mechanism

Layered double hydroxides nanoparticles (LDH NPs) composed by divalent/trivalent metal ions are efficient vaccine adjuvants to assist antigens to induce potent humoral and cellular immunity. However, the adjuvant mechanisms of LDH NPs still remains elusive. Since the metal ion species and ratio are closely related to the adjuvant activity of LDH NPs, this study will investigate how the metal ion composition will affect the adjuvant activity of LDH NPs. Then, an atomic force microscopy (AFM)-based approach to physico-mechanically map the specific interaction occurring between NP and Toll-like receptor-4 or scavenger receptor A1 in vitro on living cells. Finally, the adjuvant signaling pathways of LDH NPs will be investigated in antigen presenting cells. This study will greatly advance the knowledge on the interplay among nanomaterials and innate immunity. The single-cell, quantitative approach can be readily applied to study the binding of other nanomaterials and the testing of anti-inflammatory molecules on living cells of the innate immune system.