Enrico Rampazzo

Luminescent Chemosensors Based on Silica Nanoparticles

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).

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.

Luminescent chemosensors based on silica nanoparticles for the detection of ionic species

The field of nanoparticles is very complex and many-sided, and these versatile materials find applications in different areas going from industry, to bio-analysis, and catalysis. Within this wide framework we have focused our attention on luminescent silica nanoparticles able to act as sensing materials. We present here an overview on recent examples having ionic species as the target analyte. Our analysis tries to highlight the huge potentiality offered by these nanoarchitectures that can allow pairing and even improving many of the typical features of molecular probes in several applications.

Monofunctional stealth nanoparticle for unbiased single molecule tracking inside living cells.

On the basis of a protein cage scaffold, we have systematically explored intracellular application of nanoparticles for single molecule studies and discovered that recognition by the autophagy machinery plays a key role for rapid metabolism in the cytosol. Intracellular stealth nanoparticles were achieved by heavy surface PEGylation. By combination with a generic approach for nanoparticle monofunctionalization, efficient labeling of intracellular proteins with high fidelity was accomplished, allowing unbiased long-term tracking of proteins in the outer mitochondrial membrane.

Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies.

Multiple dye-doped NIR-emitting silica nanoparticles for both flow cytometry and in vivo imaging

Dye-doped near infrared-emitting silica nanoparticles (DD-NIRsiNPs) represent a valuable tool in bioimaging, because they provide sufficient brightness, resistance to photobleaching and consist of hydrophilic non-toxic materials. Here, we report the development of multiple dye-doped NIR emitting siNPs (mDD-NIRsiNPs), based on silica–PEG core–shell nanostructures doped with a donor–acceptor couple, exhibiting a tunable intensity profile across the NIR spectrum and suitable for both multiparametric flow cytometry analyses and time-domain optical imaging. In order to characterize the optical properties and fluorescence applications of the mDD-NIRsiNPs, we have characterized their performance by analyzing their in vivo biodistribution in healthy mice as well as in lymphoma bearing xenografts, and their suitability as contrast imaging agents for cell labeling and tracking. The mDD-NIRsiNPs features will be useful in designing new applications for imaging agents based on silica nanoparticles for different experimental disease models.

Gold nanoparticles stabilized using a fluorescent propargylic ester terminal alkyne at room temperature

Stabilized gold nanoparticles are attracting more and more the interest of the scientific community, and this is mostly due to their versatility. We present the synthesis and characterization of gold nanoparticles of a mean diameter of 5.6xa0±xa00.4xa0nm stabilized using a terminal alkyne derivative of pyrene, a fluorophore able to act as a spectrofluorimetric probe. This capping moiety, including a propargylic ester, was designed to present a good tendency to interact with the gold surface possibly forming carbenoid intermediates. Its behaviour has been compared with the one of a linear terminal alkyne, also derivatized with a pyrene moiety. The changes in the photophysical properties of pyrene unambiguously show the formation of gold nanoparticles only using the species able to perform a rearrangement, clearly indicating that this ability is crucial for binding on the nanoparticles, the rather poorly stabilizing terminal alkynes.

pH-responsive host–guest polymerization and blending

In this work, we demonstrate – in two different settings – the potential of the recognition motif made by tetraphosphonate cavitand/N-methyl ammonium salt for the development of supramolecular polymer chemistry. In the first part a novel pH sensitive supramolecular homopolymer was assembled by proper design of the corresponding monomer, and monitoring the self-assembling process by several analytical tools, including NMR spectroscopy and light scattering techniques. These measurements provided the evidence for the formation of the homopolymer and its pH responsiveness. In the second study, the two recognition groups – tetraphosphonate cavitand (Host) and sarcosine hydrochloride (Sarc) – introduced in polystyrene (PS–Host) and poly(butyl methacrylate) (PBMA–Sarc) respectively, led to the mixing of the two otherwise immiscible polymers thanks to the energetically favourable host–guest interactions between the polymer chains. The polymer blending was verified by the presence of a single glass transition temperature (Tg) and showed its homogeneous morphology by atomic force microscopy (AFM).