Applications of nanotechnology for immunology

Abstract

Nanotechnology uses the unique properties of objects that function as a unit within the overall size range of 1-1,000 nanometres. The engineering of nanostructure materials, including nanoparticles, nanoemulsions or nanotubules, holds great promise for the development of new immunomodulatory agents, as such nanostructures can be used to more effectively manipulate or deliver immunologically active components to target sites. Successful applications of nanotechnology in the field of immunology will enable new generations of vaccines, adjuvants and immunomodulatory drugs that aim to improve clinical outcomes in response to a range of infectious and non-infectious diseases.

Figure 1. Examples of nanotechnologies applied to immunoregulation.

Nanotechnologies that can be applied to immunoregulation include nanoparticles (parts a–c), nanoemulsions (parts d–f) and virus-like particles (parts g–h). Nanoparticles include dendrimers which branch out (part a), carbon molecules known as spherical fullerenes (part b) and cylindrical carbon molecules known as cylindrical fullerenes (part c). Nanoemulsions incorporate immiscible components such as oil and water that might form amphiphilic molecules such as micelles (part d), liposomes with a lipid bilayer (part e) and oil-in-water emulsions (part f). Virus-like particles are self-assembled structures composed of one or more viral capsid proteins (part g), whereas synthetic virus-like particles are self-assembled from chemically synthesized components (part h). Examples of the relationship between nanoparticle size and bioactivity are shown in (part i). PowerPoint slide

Figure 2. Mechanisms by which nanoparticles alter the induction of immune responses.

The immunostimulatory activity of nanoscale materials has been attributed to diverse mechanisms: the delivery of antigens, including particle size-dependent tissue penetration and access to the lymphatics (part a); a depot effect, which promotes the persistence, the stability, the conformational integrity and the gradual release of vaccine antigens (part b); and repetitive antigen display in which the spatial organization of the antigens on the particle surface facilitates B cell receptor (BCR) co-aggregation, triggering and activation (part c). Additional mechanisms associated with innate immune potentiation include Toll-like receptor (TLR)-dependent and TLR-independent signal transduction (not shown); cross-presentation, which is a mechanism by which exogenously acquired-antigens are processed into MHC class I pathways, caused by the nanoparticle-mediated leakage of antigens into the cytosol after they have been taken up by the phagosome (part d); and the release of soluble mediators such as cytokines, chemokines and immunomodulatory molecules that regulate the immune response (not shown). APC, antigen-presenting cell; DC, dendritic cell; ER, endoplasmic reticulum; TCR, T cell receptor. PowerPoint slide

Figure 3. Nanoscale immune activation.

Nanoscale products might have a direct immunostimulatory effect (part a) on components of the immune system, including antigen presenting cells (APCs), B cells or T cells; they might deliver compounds that result in immunostimulation (part b); or they might use both mechanisms at the same time. Direct effects include the upregulation of homing receptors such as CC-chemokine receptor 7 (CCR7) and co-stimulatory molecules including CD40, CD80 and CD86, which results in the enhanced secretion of cytokines and increased B cell and T cell activation. Enhanced delivery of antigens and adjuvants might result in apoptosis or necrosis, which enhances vaccine immunogenicity. The pathways shown are representative examples of how different nanoparticles might activate the immune system. BCR, B cell receptor; CTL, cytotoxic T cell; IFNγ, interferon-γ; IL, interleukin; MYD88, myeloid differentiation primary-response protein 88; NF-κB, nuclear factor-κB; ROS, reactive oxygen species; TCR, T cell receptor; TGFβ, transforming growth factor-β; T_H, T helper; TLR, Toll-like receptor. PowerPoint slide

Figure 4. Nanoscale immunosuppression.

Nanoscale products might have a direct immunosuppressive effect (part a) on components of the immune response, including antigen presenting cells (APCs), B cells or T cells; they might deliver compounds that result in immunosuppression (part b); or they might use both mechanisms at the same time. Direct effects include the upregulation of transforming growth factor-β (TGFβ), which results in increased cyclooxygenase 2 (COX2), prostangandin E2 (PGE2) and interleukin-10 (IL-10), and decreased B cell and T cell activity, as well as apoptosis. The delivery of immunosuppressants results in a decreased response to IL-2 with sirolimus, the downregulation of nuclear factor-κB (NF-κB) with steroids and the upregulation of forkhead box P3 (FOXP3), which results in increased regulatory T cell (T_Reg) activity when self antigens are presented in a nanoemulsion. The pathways shown are representative examples by which different nanoscale products might suppress the immune system. MYD88, myeloid differentiation primary-response protein 88; PLGA, poly(lactide-co-glycolide); T_H, T helper; TLR, Toll-like receptor; TRIF, TIR-domain-containing adaptor protein inducing IFNβ. PowerPoint slide