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Control and eventual attenuation of inflammation is important in the management of a plethora of diseases. However, suppression of inflammatory responses, e.g. by corticosteroids or systemic blockade of immune effector pathways, is associated with severe risks, including increased risk for infections, metabolic disorders and malignancies. Several drug delivery systems have recently been developed to better control the distribution of immunosuppressive drugs in the body and have yielded first promising results. However, all these approaches remain based on small molecule drugs, which eventually distribute to the systemic circulation because of their high diffusivity.
Here, we seek to explore the prospects of inorganic cerium oxide nanoparticles (CeO2, nanoceria) as self-regenerating, long-acting immunomodulators. Nanoceria has previously been shown to exhibit anti-oxidant, anti-inflammatory and antibacterial effects. The activity of the ceria is based on the microenvironment-dependent cycling of Ce3+ and Ce4+, which results in a unique redox chemistry. However, the reproducible, sterile and scalable synthesis and characterization of high-quality nanoceria has remained a major obstacle preventing comprehensive mechanistic studies. The Empa project partner has recently shown that catalytically active nanoceria can be produced in a highly controlled manner by scalable and sterile flame spray pyrolysis. In a first in vivo study, it has been shown that nanoceria preferentially accumulates in macrophages both in the liver and spleen following intravenous administration or in skin macrophages following local application to the subcutis. In this joint KSSG/Empa project, we combine the expertise in immunology of the KSSG project partner with the innovative nanoparticle design of the Empa project partner. We will assess the response of macrophages to nanoceria in vitro and in vivo to further characterize and evaluate the anti-inflammatory effects of nanoceria. In addition, we will assess how and to which extent macrophages alter their catalytic activity of nanoceria using nano-analytical characterization. The preliminary results will be used to further develop the joint activities in this area and to prepare grant applications for a project focussing on the potential use of nanoceria as a long-acting intracellular immunomodulator for local use in inflammatory diseases.