Aluminum Oxide Nanoparticles as Carriers and Adjuvants for Eliciting Antibodies from Non-immunogenic Haptens

Functionalized nanomaterials have applications yet to be discovered, especially in the biological field and, in particular, the in vivo production of antibodies. In this paper, we show that aluminum oxide nanoparticles that are covalently coupled to haptens (small molecular mass compounds) activate the immune system, eliciting antibodies (polyclonal and monoclonal) specific for the herbicide atrazine, the. antibiotic sulfasalazine, and the vitamin biotin in mice and rabbits. The particles play the role of carrier and adjuvant, with the immune response being dependent on size and crystallinity. The affinity constants of the antibodies are similar to those reached with traditional immunization strategies based on the use of carrier proteins. This approach has not been previously described, being of scientific and practical interest, as it can lead to immunogens safer than the conventional ones, potentially applicable to human vaccination. In addition, the useful advantages of this technique include the stability of the metallic particles, the synthesis of immunogens in organic media, the versatility of particle derivatization, the ease of purification, the full chemical characterization of immunogens, the lack of a requirement for an adjuvant, the reduction of the cross reactivity, and the low cost of materials. Also, the analytical performances of the immunoassays developed using these antibodies are comparable to those obtained by the standard protocols. Analytical applications of the developed ELISAs were fully demonstrated. Characterization (IgG nature, affinity constants, etc.) of the immunoreagents were also fully assessed.