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Marco Soster,1,* Riccardo Juris,2,* Sara Bonacchi,2 Damiano Genovese,2 Marco Montalti,2 Enrico Rampazzo,2 Nelsi Zaccheroni,2 Paolo Garagnani,2 Federico Bussolino,3,4 Luca Prodi,2 Serena Marchiò1,4 1Institute for Cancer Research and Treatment, Laboratory of Tumor Microenvironment and University of Torino, Department of Oncological Sciences, Candiolo, 2University of Bologna, Department of Chemistry "G.Ciamician", Bologna, 3Institute for Cancer Research and Treatment, Laboratory of Vascular Oncology and University of Torino, Department of Oncological Sciences, Candiolo, 4APAvadis Biotechnologies, BioIndustry Park S Fumero, Colleretto Giacosa, Italy*These authors equally contributed to the workBackground and methods: Despite the recent introduction of targeted bio-drugs, the scarcity of successful therapeutic options for advanced colorectal cancer remains a limiting factor in patient management. The efficacy of curative surgical interventions can only be extended through earlier detection of metastatic foci, which is dependent on both the sensitivity and specificity of the diagnostic tools.Results: We propose a high-performance imaging platform based on silica-poly(ethylene glycol) nanoparticles doped with rhodamine B and cyanine 5. Simultaneous detection of these dyes is the basis for background subtraction and signal amplification, thus providing high-sensitivity imaging. The functionalization of poly(ethylene glycol) tails on the external face of the nanoparticles with metastasis-specific peptides guarantees their homing to and accumulation at target tissues, resulting in specific visualization, even of submillimetric metastases.Conclusions: The results reported here demonstrate that our rationally designed modular nanosystems have the ability to produce a breakthrough in the detection of micrometastases for subsequent translation to clinics in the immediate future.Keywords: colorectal cancer, imaging platform, luminescent targeting, micrometastasis, peptide targeting

Biocompatible highly bright silica nanoparticles were designed, prepared and tested in small living organisms for both in vivo and ex vivo imaging. The results that we report here demonstrate that they are suitable for optical imaging applications as a possible alternative to commercially available fluorescent materials including quantum dots. Moreover, the tunability of their photophysical properties, which was enhanced by the use of different dyes as doping agents, constitutes a very important added value in the field of medical diagnostics.

Silica nanoparticles are versatile platforms with many intrinsic features, such as low toxicity. Proper design and derivatization yields particularly stable colloids, even in physiological conditions, and provides them with multiple functions. A suitable choice of dyes and synthetic strategy may, in particular, yield a very bright nanosystem. Silica nanoparticles thus offer unique potential in the nanotechnology arena, and further improvement and optimization could substantially increase their application in fields of high social and economic impact, such as medical diagnostics and therapy, environmental and food analysis, and security. This paper describes silica-based, multicomponent nanosystems with intrinsic directional energy- and electron- transfer processes, on which highly valued functions like light harvesting and signal amplification are based.

The field of nanoparticles is amazingly many-sided and consequently their applications range between many different areas from industry to bio-analysis and catalysis. In particular, luminescent nanoparticles attract close attention in the areas of biology, medical diagnosis and therapy, where they already find many applications. In this so fascinating and wide framework we have focussed our attention on luminescent silica nanoparticles able to act as sensing materials. We highlight here the importance, especially with the aim of sensing, of gaining precise knowledge and control of their structures; the performance of a chemosensor is, in fact, totally dependent on its design. We then briefly present the state of the art and the progress both in the synthetic protocols and in the application of luminescent silica nanoparticles as chemosensors. We present many recent examples, organized into two main sections, the first dealing with systems presenting the signalling units on the surface (dye coated silica nanoparticles, DCSNs) and the second with systems entrapping the dyes inside the silica matrix (dye doped silica nanoparticles, DDSNs).

The design of fluorescent chemosensors for biologicallyrelevant chemical species has important impacts in many ap-plications, and for this reason it has been the subject ofactive research in many laboratories worldwide. The ach-ievements in this wide research topic have promoted enor-mous steps forwards, for example, in the field of cell biology,thanks to the comprehension of the role of different chemi-cal species in many biological processes. Recently, research-ers have been moving from molecular chemosensors basedon two communicating units, a receptor and a dye, towardmore complex and sophisticated structures, and have triedto push further the limits of sensitivity and selectivity. Manydifferent solutions have been proposed but, among them,sensing systems based on nanoparticles are certainly one ofthe most interesting and promising.

Electronic energy transfer is a crucial photophysical process, since it is at the basis of essential natural phenomena such as photosynthesis, as well as of widely spread artificial molecular devices; moreover, it is a very valuable tool for measuring distances at the nanometer level. For artificial systems, the possibility to take profit of energy transfer processes has enormously increased with the advent of supramolecular chemistry,1 and a new additional boost is expected to be observed with the very rapid growth of nanotechnology, in many different fields, ranging from medical diagnostics to solar energy conversion. In the context of nanotechnology, a great and increasing interest is devoted to nanoparticles.2 Nanoparticles can be made of many different materials, including polymers, metals, semiconductors, or a combination of them. Their versatility and different properties have already gained them many industrial applications in a wide range of fields, such as electronics, medicine and material sciences. One of the cut-edge fields in nanoparticle research is the enhancement of biological imaging for medical diagnostics and drug delivery. In this article, we will focus our attention on the potentialities offered by the use of energy transfer processes in dye-doped or dye-coated silica nanoparticles (DDSN or DCSN respectively),3-10 which conjugate a simple and low-cost preparation with the possibility to obtain sophisticated, but robust, multifunctional systems, especially when they are designed as ‘onion-like’, multilayer structures. The design of these systems is not trivial and it has to be carefully studied to be able to foresee the photophysical characteristics of the resulting materials. On the other hand, despite the complexity of these systems, their synthesis is relatively simple and very versatile. These features make them a very powerful tool to obtain very complex and precious functions from low cost and easy to prepare nanoobjects. In the next paragraphs we will present the most common synthetic strategies to obtain dye doped and dye covered silica nanoparticles and discuss many examples, but we would like to start introducing the energy transfer process and its great scientific and applicative importance.