Despite standard treatment, the prognosis of glioblastoma patients remains dismal. New therapies, like dendritic cell (DC) immunotherapy, are emerging to overcome the limitations of the current treatment. Multiple groups use this treatment strategy and observe long term survival in several patients. Important disadvantages of this patient customized therapy are its high cost and limited efficacy.
Based on our preliminary results from in vivo studies with polystyrene nanoparticles (NPs), the use of NPs may provide a solution. We report the production of biodegradable mesoporous silica NPs (MSNPs), which can be used as a vaccine carrier to stimulate the adaptive immune system. In a first stage, the NP synthesis and functionalization were optimized. These consist of a one pot wet chemistry process which can easily be upscaled to industrial production. After assessing the physicochemical properties with a broad range of characterization tools, the effect of synthesis parameters on the biodegradability of the NPs was determined using molybdenum blue chemistry. In a second stage, ovalbumin was used as a model antigen and loaded on the MSNPs with carbodiimide crosslinker chemistry. The nanovaccine was tested in vitro on DCs to examine the toxicity, uptake, maturation effect and the potential immunogenicity. In the final stage, the vaccine was administered in vivo in mice and the the T-cell populations from the splenocytes were examined.
The NPs were successfully functionalized and determined to be stable at physiological pH. The degradation behavior was shown to be strongly dependent on the synthesis parameters and could be varied from a few hours to a week. Additionally, the DCs were able to take up the MSNPs, as well as the nanovaccine. This uptake was determined to be an active process. Moreover, it was shown that the nanovaccine could induce maturation of DCs, which is a strong indication that MSNP vaccines could have an adjuvant effect on the DCs and perhaps the adaptive immune response. Moreover, it was found that DCs treated with the nanovaccine were able to cross-present the ovalbumin antigen in significantly higher amount than control conditions. Finally, spleens collected from nanovaccine immunized mice showed higher T-cell proliferation after in vitro stimulation as compared to mice immunized with ovalbumin alone. These preliminary results show that MSNPs can be studied further as carrier in the production of antitumor nanovaccines.