Nanotechnology-based Strategies to Modulate Immune Responses

Nanotechnology has shown an important potential in the immunotherapeutic field, as the modulation of a variety of immune processes can be achieved both in vitro and in vivo. Nanotechnology can be used to promote the immune activation or to induce tolerance depending on the nanocarrier composition and its physicochemical properties. The use of ligands for specific cell receptors could substantially increase the targeting to a particular subset of immune cells, and the combination of nanoparticles with other immunomodulators may constitute a useful strategy to effectively polarize the immune response.

Treatments based on the modulation of the immune system is a field in expansion where the contribution of nanotechnology is growing exponentially [1], as it represents a new way of communication with the immune system. Nanocarrier characteristics such as the composition, physicochemical properties, size and the presence of molecules involved in immune processes [2] can influence the immune system behavior by reinforcing either its activation in order to generate a response against a specific pathogen, or the induction of immunotolerance against antigens and immunoactive drugs. The first mechanism improves the control of infectious diseases and cancer, whereas the second refers to the development of vaccines against autoimmune diseases as well as the targeted administration of immunomodulatory drugs [3]. In this context, nanotechnology means versatility.

Different routes for nanoparticle delivery to different immune system subsets. Dacoba, T. G., et al. Modulating the immune system through nanotechnology. Seminars in immunology, 2017, 34, 78–102.

Nanoparticles (NPs) should be specifically engineered to go preferentially to the target tissue from the site of administration. As the key cells involved in immunity are concentrated in the lymphoid tissues, targeting nanoparticles to them will facilitate the access to immune cells and increase the efficacy of administered NPs. There are two main administration ways for NPs: mucosal or parenteral. Following mucosal administration, NPs can either induce mucosal responses due to the activation of mucosal resident T [4] and B [5] cells or generate a tolerance reaction [6]. NPs first overcome the mucus layer that cover the mucosal surfaces and then are either transported by M cells or epithelial cells, internalized by paracellular transport, or taken up by dendritic cells (DCs) that extent their dendrites into the lumen. Designing a proper NP composition that allows its interaction with cells within the mucosal surface has been a hot topic in recent years. In contrast, by parenteral administration NPs can drain directly to the closest lymph node (LN) or stay in the injection site to attract migratory DCs or macrophages. NPs up to 100 nm are able to self-drain to the nearest LN, being the drainage inversely proportional to the particle size [7], and particles smaller than 10 nm can directly drain to blood capillaries, showing no retention when reaching the LNs [8]. All the experimentation with NPs points that their final outcome is determined by the simultaneous influence of the particle size, surface charge, shape, hydrophobicity and stiffness, among others.