Cytostatic and Cytotoxic Effects of Hollow-Shell Mesoporous Silica Nanoparticles Containing Magnetic Iron Oxide.

Among the different types of nanoparticles used in biomedical applications, Fe nanoparticles and mesoporous siliceous materials have been extensively investigated because of their possible theranostic applications. Here, we present hollow-shell mesoporous silica nanoparticles that encapsulate iron oxide and that are prepared using a drug-structure-directing agent concept (DSDA), composed of the model drug tryptophan modified by carbon aliphatic hydrocarbon chains. The modified tryptophan can behave as an organic template that allows directing the hollow-shell mesoporous silica framework, as a result of its micellisation and subsequent assembly of the silica around it. The one-pot synthesis procedure facilitates the incorporation of hydrophobically stabilised iron oxide nanoparticles into the hollow internal silica cavities, with the model drug tryptophan in the shell pores, thus enabling the incorporation of different functionalities into the all-in-one nanoparticles named mesoporous silica nanoparticles containing magnetic iron oxide (Fe3O4@MSNs). Additionally, the drug loading capability and the release of tryptophan from the silica nanoparticles were examined, as well as the cytostaticity and cytotoxicity of the Fe3O4@MSNs in different colon cancer cell lines. The results indicate that Fe3O4@MSNs have great potential for drug loading and drug delivery into specific target cells, thereby overcoming the limitations associated with conventional drug formulations, which are unable to selectively reach the sites of interest.

Engineering hollow mesoporous silica nanoparticles to increase cytotoxicity.

Hollow mesoporous silica nanoparticles (HMSNs) consist of a network of cavities confined by mesoporous shells that have emerged as promising tools for drug delivery or diagnostic. The physicochemical properties of HMSNs are dictated by the synthesis conditions but which conditions affect which property and how it impacts on biological interactions is unclear. Here by changing the concentration of the structure-directing agent (SDA), the pH and the ratio between SDA and added salt (NaCl) we determine the effects in size, morphology, surface charge and density or degree of compaction (physicochemical properties) of HMSNs and define their impact on their biological interactions with human colon cancer or healthy cells at the level of cellular uptake and viability. Increased size or density/degree of compaction of HMSNs increases their cytotoxicity. Strikingly, high salt concentrations in the synthesis medium leads to a spiky-shell morphology that provokes nuclear fragmentation and irreversible cell damage turning HMSNs lethal and unveiling intrinsic therapeutic potential. This strategy may open new avenues to design HMSNs nanoarchitectures with intrinsic therapeutic properties without incorporation of external pharmaceutical ingredients.

One-dimensional migration of olfactory ensheathing cells on synthetic materials: experimental and numerical characterization.

Olfactory ensheathing cells (OECs) are of great interest for regenerative purposes since they are believed to aid axonal growth. With the view set on the strategies to achieve reconnection between neuronal structures, it is of great importance to characterize the behaviour of these cells on long thread-like structures that may efficiently guide cell spread in a targeted way. Here, rat OECs were studied on polycaprolactone (PCL) long monofilaments, on long bars and on discs. PCL turns out to be an excellent substrate for OECs. The cells cover long distances along the monofilaments and colonize completely these structures. With the help of a one-dimensional (1D) analytical model, a migration coefficient, a net proliferation rate constant and the fraction of all cells which undergo migration were obtained. The separate effect of the three phenomena summarized by these parameters on the colonization patterns of the 1D path was qualitatively discussed. Other features of interest were also determined, such as the speed of the advance front of colonization and the order of the kinetics of net cell proliferation. Characterizing migration by means of these quantities may be useful for comparing and predicting features of the colonization process (such as times, patterns, advance fronts and proportion of motile cells) of different cell-substrate combinations.

Fibronectin distribution on demixed nanoscale topographies.

PURPOSE: It is known that surface nanotopography influences cell adhesion and differentiation. Our aim is to analyze the effect of nanoscale topography on fibronectin adsorption and, afterwards, on cell adhesion in order to rationalize the cell-material interaction by focusing on the state of the intermediate layer of adsorbed fibronectin at the material interphase. METHODS: Nanotopographic surfaces were produced by demixing of thin film polymer blends - PLLA and PS - during a high speed spin-casting process. Fibronectin (FN) was adsorbed on the different nanotopographies and the protein distribution was directly observed by atomic force microscopy (AFM). The fraction of the surface covered by the protein was quantified by image analysis, as well as the distribution of FN between peaks and valleys. Focal adhesion protein -vinculin- was immunostained and quantified by image analysis on the different nanoscale surfaces. RESULTS: Different nanoscale domains were obtained by changing the composition of the system within a height range of 3 nm to 30 nm. FN tends to adsorb on the peaks of nanoisland topographies, especially in compositions that did not enhance cell adhesion. Moreover, protein distribution between valleys and peaks alters the size of focal adhesion plaques, which grew larger on surfaces with an even distribution of fibronectin. CONCLUSIONS: Our results suggest that the surface nanotopography is a key material property capable of influencing protein adsorption. Additionally, the distribution of the protein on the different samples was correlated to the initial ability of cells to adhere in terms of the size of the focal plaques.