Study and development of self-propelled nanomotors for anti-inflammatory therapy

Inflammation is the body's normal response to pathogenic infection or tissue damage and is crucial to the healing process. Inflammation occurs in response to injury or infection to protect the host from pathogens and heal damaged tissue, supporting in the re-establishing of the body's balance. In general, inflammation happens in a series of steps which start with a rapid induction phase that leads to a pro-inflammatory response, followed by a resolution phase. Inflammation is essential for the healing of wounds, however, if the response is not controlled, it can become chronic and out of control, triggering the development and progression of a variety of inflammatory diseases, including cancer, obesity, sepsis, cardiovascular, neuronal, and autoimmune diseases. The main players involved in chronic inflammation consist of macrophages, specifically proinflammatory M1-type macrophages. These cells participate in host defence by destroying and ingesting harmful substances to limit and prevent damage to the organism. They exert their proinflammatory functions by producing high levels of proinflammatory cytokines, reactive oxygen species (ROS), inducible nitric oxide synthase (INOS), cyclooxygenase (COX)-2, and reactive nitrogen species (H2O2). Therefore, one of the ways to deal with the problem of chronic inflammation could be to intervene on this cell type, taking advantage of its main function, the internalisation of foreign bodies. Innovative drug delivery methods based on nanoparticles have been proposed as suitable drug delivery systems, which can provide sustained release and can improve target specificity, drug half-life and diffusion. In this context, self-propelled nanoparticles with active movement (nanomotors) in response to catalysis of different fuels such as H2O2 are a promising tool to deliver drugs to hard-to-reach diseased areas. However, most nanodevices rely on high concentrations of toxic and exogenous fuels, which limits their application in the biomedical field. Therefore, it is interesting to investigate and develop nanomotors powered by endogenous substances already present at high level, such as H2O2, in therapeutically relevant areas. The aim of the work in this thesis is to focus on the synthesis, characterisation, and evaluation of Janus nanomotors consisting of mesoporous silica, the anti-inflammatory drug dexamethasone, and a redox-sensitive molecular gate, in order to achieve enhanced drug release for anti-inflammatory therapy. Numerous investigations have been conducted to investigate and validate the morphology, porosity and proper function of the synthesised nanomotors.