Nanomedicine seeks to apply nanoscale materials for the therapy and diagnosis of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery of therapeutic agents only to the specific site. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in a discreet manner and interact with cells/tissues only locally. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems - theranostics - holds great promise to minimise side effects and boost therapeutic effectiveness of the treatment. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides a comprehensive review of the state-of-the-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications.

The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO 2 ), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO 2 on gut microbiota of mice when orally administered via drinking water. While TiO 2 had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO 2 treatment could alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO 2 significantly impacts gut homeostasis. These changes were associated with colonic inflammation, as shown by decreased crypt length, infiltration of CD8 + T cells, increased macrophages as well as increased expression of inflammatory cytokines. These findings collectively show that TiO 2 is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.

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Titanium dioxide (TiO 2 ) nanoparticles are used industrially and commercially at increasingly high levels. While toxicity is addressed prior to use, it is also important to consider the cellular response to these nanoparticles at subcytotoxic concentrations. We used PCR arrays to screen for changes to 84 different oxidative stress-related genes in response to the incubation of cells with TiO 2 nanoparticles. We found that expression of four members of the peroxiredoxin family of antioxidant enzymes was altered in response to the TiO 2 nanoparticles. The oxidative stress response was specific to TiO 2 nanoparticles; polystyrene nanoparticles did not alter the expression of the peroxiredoxins. In addition, serum proteins adsorbed on the surface of the TiO 2 nanoparticles had a protective effect. In the absence of serum proteins, TiO 2 nanoparticles were cytotoxic at the same concentrations. These experiments demonstrate that protein−TiO 2 nanoparticle complexes lead to a unique oxidative stress response in cells. More broadly, these experiments point to the importance of examining the cellular response to nanoparticles at low concentrations that do not lead to cytotoxicity but may cause more subtle cellular changes.

An innovative high-resolution nano-bio-spectroscopy approach to identify nanoscale differences in the structural composition of individual stem cell-derived extracellular vesicles.