Understanding the Effect of Surface Chemistry of Mesoporous Silica Nanorods on Their Vaccine Adjuvant Potency

Abstract

Mesoporous silica nanoparticles are reported as adjuvants in nanovaccines in generating robust antigen-specific immunity. However, the effect of surface chemistry in initiating and modulating the immune response remains largely unexplored. In this study, mesoporous silica nanorods (MSNRs) are modified with NH and C groups to investigate the influence of surface functional groups (OH, NH , and C ) on their adjuvant efficacy. It is found that compared to OH and NH groups, the hydrophobic C modification significantly enhances antigen uptake by antigen presenting cells and endosomal-lysosomal escape in vitro, dendritic cells, and macrophages maturation ex vivo, and elicits secretion of interferon-γ level and antibody response in immunized mice. Moreover, bare MSNR and MSNRNH exhibit T-helper 2 biased immune response, while MSNRC shows a T-helper 1 biased immune response. These findings suggest that the surface chemistry of nanostructured adjuvants has profound impact on the immune response, which provides useful guidance for the design of effective nanomaterial based vaccines.

Materials for Immunotherapy

“…First, the Mooney group modified the microrods with PEG, PEG‐RGD, and PEG‐RDG polymer‐peptide conjugates . Second, the Yu group modified the microrods with –NH 2 and –C18 groups to investigate the influence of surface functional groups compared to the native –OH . Both groups discovered that surface modification plays a major role in altering the inherent inflammatory response, leukocyte infiltration profile, and ultimately vaccine potency.…”

“…[435] Second, the Yu group modified the microrods with -NH 2 and -C18 groups to investigate the influence of surface functional groups compared to the native -OH. [436] Both groups discovered that surface modification plays a major role in altering the inherent inflammatory response, leukocyte infiltration profile, and ultimately vaccine potency. In one study in 2018, the Mooney group adsorbed PEI to the surfaces of mesoporous silica microrods to enhance antigen immunogenicity via increased dendritic cell activation and CTL responses.…”

Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy

“…Surface functional groups are another factor related to the activation level of DCs. The effect of OH, NH 2 , and C 18 functional groups on SBA‐15 type mesoporous silica nanorods (MSNRs) on DC activation and maturation were investigated after loading of ovalbumin (OVA) protein in the particles (Figure D) . There was no significant difference in CD40 expression among all conditions.…”

“…Different functional groups of mesoporous silica can tune the type of immune response. MSNRs 50–200 nm in length and 10–30 nm in diameter were used to induce immunomodulation by altering the natural OH group of MSNRs with NH 2 and C 18 groups . Because of hydrophobic interaction between OVA and C 18 groups, antigen accumulation in MSNR‐C 18 was prolonged.…”

“…Loading immune modulating molecules into those materials can protect the molecules from rapid removal and degradation in the body and allow favorable delivery of molecules to target sites such as lymph nodes, immune cells, and tumor sites, which lead to the enhanced therapeutic efficacy of materials‐based immunotherapy. Several types of engineered immunomodulatory materials have been developed and their immunomodulatory effects have been demonstrated in diverse platforms, such as poly(lactide‐ co ‐glycolide) (PLG) nanoparticles, PLG scaffolds, carbon‐based nanoparticles, gold nanoparticles, liposomes, mesoporous silica, and other materials …”