Abstract
Nanoparticles may be used in vaccinology as an antigen delivery and/or an immunostimulant to enhance immunity. Porous silica has been identified as an effective adjuvant for more than a decade, and we have therefore investigated the take up rate by an immortalized macrophage-like cell line of a number of mesoporous silica nanoparticles (MSNPs) with differing diameter and pore size. The MSNPs were synthesized using a sol-gel reaction and post-synthesis removal of the template. The MSNPs showed a clear distribution in take up rate peaking at 217 nm, whereas a comparison with solid spherical nanoparticles showed a similar distribution peaking at 377 nm. The MSNPs were investigated before and after loading with antigen. Diphtheria toxoid was used as a proof-of-concept antigen and showed a peak macrophage internalization of 53.42% for loaded LP3 particles which had a diameter of 217.75 ± 5.44 nm and large 16.5 nm pores. Optimal MSNP sizes appeared to be in the 200–400 nm range, and larger pores showed better antigen loading. The mesoporous silica particles were shown to be generally biocompatible, and cell viability was not altered by the loading of particles with or without antigen.Graphical abstract
Highlights
Nanovaccinology involves the use of nanometre sized particles as a means to deliver antigen, in order to enhance antigen processing
To assess the uptake of the different silica nanoparticles, and to determine whether this was affected by size, porosity or loading, we tested the ability of the particles to be taken up into macrophage-like cells
We investigated a range of sizes of silica nanoparticles to determine the effect on uptake by THP-1 macrophage-like cells
Summary
Nanovaccinology involves the use of nanometre sized particles as a means to deliver antigen, in order to enhance antigen processing. A variety of engineered nanoparticles have been developed for vaccine development and while they differ in size, shape and composition, they are typically 25–200 nm in diameter (Zhao et al 2014). The large surface area to volume ratio of nanoparticles means that the particles may carry a higher proportion of antigen for immune activation. The size of the nanoparticle systems increases the likelihood that they will accumulate in lymph nodes. This can both increase their effective concentration and reduce systemic reactivity (Nuhn et al 2016). Our previous work compared the antigen loading and unloading capacity of mesoporous silica nanoparticles (MSNPs), with a variety of different pore sizes, and external diameters (Huang et al submitted). The uptake of nanoparticles, and subsequent immune response, may be due to their intrinsic resemblance to natural viruses
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