Concentration and distribution of silica nanoparticles in colon cancer cells assessed by synchrotron based X-ray techniques.

The quantitative uptake of Silica nanoparticles (SiNPs), although representing an essential prerequisite for their theranostic use, is difficult to address and it is still not utterly investigated. In this study, we tested the uptake and toxicity of two different types of luminescent core-shell silica-PEG (polyethylene glycol) nanoparticles SiNP and their carboxylate analogues on human adenocarcinoma cell line LoVo. We assessed the intracellular spatial distribution and concentration of Si element in the cell by a state-of-the-art approach merging synchrotron-based X-ray techniques (XRFM) with scanning transmission X-Ray microscopy (STXM). The concentration maps of Si obtained reflect the distribution of the SiNPs. In addition, we calculated the number of SiNPs per volume unit in each single cell, quantitating the exact amount of conveyed particles. The absence of effects on proliferation and cell death was confirmed by viability assays, morphological analysis and cytofluorimetric evaluation of ROS content. The three-dimensional analysis of intracellular uptake of both types of nanoparticles (with different surface charge) was performed by confocal fluorescence microscopy, which showed a main localization in the cytosolic region with no sign of nuclear uptake.

Systematic approach in Mg2+ ions analysis with a combination of tailored fluorophore design.

A systematic study of a series of diaza-18-crown-6 8-hydroxyquinoline (DCHQ) chemosensors, devoted to Mg(II) ion detection, was performed. Functionalization of DCHQ by peripheral substituents allowed the development of novel all-solid-state optodes via inclusion inside PVC-based polymeric films. The influence on the DCHQ-based optode response of the lipophilic sites functionalization and of the nature of the plasticizer, was investigated. Fluorimetric studies on optodes sensitivity towards a number of different metal cations (Ca2+, Na+, K+, Li+, Co2+, Cd2+, Pb2+, Cu2+, Hg2+, Zn2+) and NH4+ were carried out. The results demonstrated the suitability of the DCHQ optodes to perform fast monitoring (<10s) of magnesium (II) ions. Emission light signal was sufficiently brilliant to be captured by a low-cost computer webcam. The phenyl-substituted DCHQ-Ph derivative showed the best performance with a wide range for Mg(II) ion determination between 2.7 × 10-7 and 2.2 × 10-2 mol/L. It was possible, therefore, to determine the concentrations of Mg(II) in commercial fertilizer samples by DCHQ-Ph-based optodes with acceptable results: recoveries of 96.2-104.9% and relative standard deviation (RSD, n = 6) less than 5%. Moreover, in comparison to single sensors, the use of an array composed of five optodes (the ones showing the best performances in the preliminary tests) has allowed to reduce the RSD of magnesium determination in real samples (down to 3.7% with respect to 5.5% for single optodes) and to achieve a detection limit (estimated by s/n = 3 method) as low as 4.6 × 10-7 mol/L.

Imaging agents based on lanthanide doped nanoparticles.

Nanotechnology has recently allowed us to design and prepare nanoplatforms with the potential to face currently unresolved problems. Among these platforms, nanoparticles in particular are versatile objects that find applications in many different areas. In the vast ensemble of materials that have been explored to obtain nanoparticles with improved performances, we here focus our attention on lanthanide-based nanocrystals. These recently developed species are extremely interesting and well known particularly for their ability to emit anti-Stokes shifted light (upconversion) with relatively high brightness. Many advantageous characteristics of such materials are emerging, and their use as multimodal imaging agents is rapidly growing. We here survey some recent examples on this subject, mainly focusing on systems having NIR-to-NIR emission properties for in vivo applications.

Dye-doped silica nanoparticles as luminescent organized systems for nanomedicine.

The ability to find synergic solutions is the core of scientific research and scientific advancement. This is particularly true for medicine, where multimodal imaging and theranostic tools represent the frontier research. Nanotechnology, which by its very nature is multidisciplinary, has opened up the way to the engineering of new organized materials endowed with improved performances. In particular, merging nanoparticles and luminescent signalling can lead to the creation of unique tools for the design of inexpensive, hand-held diagnostic and theranostic kits. In this wide scenario, dye-doped silica nanoparticles constitute very effective nanoplatforms to obtain efficient luminescent, stable, biocompatible and targeted agents for biomedical applications. In this review we discuss the state of the art in the field of luminescent silica-based nanoparticles for medical imaging, starting with an overview of the most common synthetic approaches to these materials. Trying to rationalize the presentation of this extremely multifaceted and complex subject, we have gathered significant examples of systems applied in cancer research, also discussing those that take a multifunctional approach, including theranostic structures. Nanoprobes designed for applications that do not include cancer are a minor part, but interesting achievements have been published and we present a selection of these in the subsequent section. To conclude, we propose a debate on the advantages of creating chemosensors based on luminescent silica nanoparticles. This is far from easy but is a particularly valuable goal in the medical field and therefore subject to extensive research worldwide.

Luminescent silica nanoparticles for cancer diagnosis.

Fluorescence imaging techniques are becoming essential for preclinical investigations, necessitating the development of suitable tools for in vivo measurements. Nanotechnology entered this field to help overcome many of the current technical limitations, and luminescent nanoparticles (NPs) are one of the most promising materials proposed for future diagnostic implementation. NPs also constitute a versatile platform that can allow facile multi-functionalization to perform multimodal imaging or theranostics (simultaneous diagnosis and therapy). In this contribution we have mainly focused on dye doped silica or silica-based NPs conjugated with targeting moieties to enable imaging of specific cancer cells. We also cite and briefly discuss a few non-targeted systems for completeness. We summarize common synthetic approaches to these materials, and then survey the most recent imaging applications of silica-based nanoparticles in cancer. The field of theranostics is particularly important and stimulating, so, even though it is not the central topic of this paper, we have included some significant examples. We conclude with a short section on NP-based systems already in clinical trials and examples of specific applications in childhood tumors. This review aims to describe and discuss, through focused examples, the great potential of these materials in the medical field, with the aim to encourage further research to implement applications, which today are still rare.

Heterosupramolecular chemistry: programmed pseudorotaxane assembly at the surface of a nanocrystal.

Gold nanocrystals, stabilized by thiols covalently bound to a dibenzo[24]crown-8 moiety, have been programmed to recognize and selectively bind dibenzylammonium cations in solution. This results in a self-organization process at the surface of a nanocrystal with the assembly of a pseudorotaxane (see picture).