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PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization.

NanoChlor, a nanoparticle-based fluorescent probe for chloride that is both ratiometric and capable of spontaneously penetrating neuronal cells at submillimolar concentrations, was designed and studied. NanoChlor is built on silica nanoparticles grafted with 6-methoxyquinolinium as the chloride-sensitive component and fluorescein as the reference dye. A Stern-Volmer constant of 50 M(-1) was measured in Ringer's buffer at pH 7.2, and the response to chemically induced chloride currents was recorded in real time in hippocampal cells.

Fluorescent chemosensors are chemical systems that can detect and signal the presence of selected analytes through variations in their fluorescence emission. Their peculiar properties make them arguably one of the most useful tools that chemistry has provided to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In its simplest design, a fluorescent chemosensor is composed of a fluorescent dye and a receptor, with a built-in transduction mechanism that converts recognition events into variations of the emission properties of the fluorescent dye. As soon as fluorescent nanoparticles became available, several applications in the field of sensing were explored. Nanoparticles have been used not only as better-performing substitutes of traditional dyes but also as multivalent scaffolds for the realization of supramolecular assemblies, while their high surface to volume ratio allows for distinct spatial domains (bulk, external surface, pores and shells) to be functionalized to a comparable extent with different organic species. Over the last few years, nanoparticles proved to be versatile synthetic platforms for the implementation of new sensing schemes.

Nanosized objects made of various materials are gaining increasing attention as promising vehicles for the delivery of therapeutic and diagnostic agents for cancer. Photodynamic therapy (PDT) appears to offer a very attractive opportunity to implement drug delivery systems since no release of the sensitizer is needed to obtain the therapeutic effect and the design of the nanovehicle should be much easier. The aim of our study was to investigate the use of organic-modified silica nanoparticles (NPs) for the delivery of the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC) to cancer cells in vitro. mTHPC was entrapped in NPs (approximately 33 nm diameter) in a monomeric form which produced singlet oxygen with a high efficiency. In aqueous media with high salt concentrations, the NPs underwent aggregation and precipitation but their stability could be preserved in the presence of foetal bovine serum. The cellular uptake, localization and phototoxic activity of mTHPC was determined comparatively in human oesophageal cancer cells after its delivery by the NPs and the standard solvent ethanol/poly(ethylene glycol) 400/water (20:30:50, by vol). The NP formulation reduced the cellular uptake of mTHPC by about 50% in comparison to standard solvent while it did not affect the concentration-dependent photokilling activity of mTHPC and its intracellular localization. Fluorescence resonance energy transfer measurements, using NPs with mTHPC physically entrapped and a cyanine covalently linked, and ultracentrifugation experiments indicated that mTHPC is transferred from NPs to serum proteins when present in the medium. However, the coating of the NP surface with poly(ethylene glycol) largely prevented the transfer to proteins. In conclusion, mTHPC is rapidly transferred from the uncoated nanoparticles to the serum proteins and then internalized by the cells as a protein complex, irrespective of its modality of delivery.