Two-dimensional layered double hydroxide nanoadjuvant: recent progress and future direction

Layered double hydroxide (LDH) is a 'sandwich'-like two-dimensional clay material that has been systematically investigated for biomedical application in the past two decades. LDH is an alum-similar adjuvant, which has a well-defined layered crystal structure and exhibits high adjuvanticity. The unique structure of LDH includes positively charged layers composed of divalent and trivalent cations and anion-exchangeable interlayer galleries. Among the many variants of LDH, MgAl-LDH (the cationic ions are Mg2+ and Al3+) has the highest affinity to antigens, bioadjuvants and drug molecules, and exhibits superior biosafety. Past research studies indicate that MgAl-LDH can simultaneously load antigens, bioadjuvants and molecular drugs to amplify the strength of immune responses, and induce broad-spectrum immune responses. Moreover, the size and dispersity of MgAl-LDH in biological environments can be well controlled to actively deliver antigens to the immune system, realizing the rapid induction and maintenance of durable immune responses. Furthermore, the functionalization of MgAl-LDH nanoadjuvants enables it to capture antigens in situ and induce personalized immune responses, thereby more effectively overcoming complex diseases. In this review, we comprehensively summarize the development and application of MgAl-LDH nanoparticles as a vaccine adjuvant, demonstrating that MgAl-LDH is the most potential adjuvant for clinical application.