Luminescent Silica Nanoparticles Featuring Collective Processes for Optical Imaging

The field of nanoparticles has successfully merged with imaging to optimize contrast agents for many detection techniques. This combination has yielded highly positive results, especially in optical and magnetic imaging, leading to diagnostic methods that are now close to clinical use. Biological sciences have been taking advantage of luminescent labels for many years and the development of luminescent nanoprobes has helped definitively in making the crucial step forward in in vivo applications. To this end, suitable probes should present excitation and emission within the NIR region where tissues have minimal absorbance. Among several nanomaterials engineered with this aim, including noble metal, lanthanide, and carbon nanoparticles and quantum dots, we have focused our attention here on luminescent silica nanoparticles. Many interesting results have already been obtained with nanoparticles containing only one kind of photophysically active moiety. However, the presence of different emitting species in a single nanoparticle can lead to diverse properties including cooperative behaviours. We present here the state of the art in the field of silica luminescent nanoparticles exploiting collective processes to obtain ultra-bright units suitable as contrast agents in optical imaging and optical sensing and for other high sensitivity applications

The influence of fluorescent silica nanoparticle surface chemistry on the energy transfer processes with lipid bilayers

Multifunctional nanoparticles (NPs) are an advantageous scaffold for assembling hybrid bio-inorganic nanoplatforms, with impact on key technologies, including molecular diagnostics, therapeutics, bioengineering, biocatalysis, energy generation and storage. In the present work we used core-shell silica NPs, coumarin-doped in the core and surface-tailored with different chemical moieties (-PEG, -COOH, -NH2), as a possible nanocarrier for drug delivery and imaging. The nanoparticle surface was further decorated with lipid bilayers by the interaction with fluorescent small unilamellar lipid vesicles bearing different charges, namely zwitterionic (PC), anionic (PS25) and cationic (EPC25). The fluorescence energy transfer (FRET) processes between the silica nanoparticles and the lipid bilayers, dye-labelled with nitrobenzoxadiazole and/or rhodamine fluorescent moieties, were investigated to exploit the behaviour of the hybrid biomembrane-NP assembly as a theranostic nanocarrier. A relevant role of electrostatic interactions to influence the photophysical properties of the hybrid lipid-NP systems resulted. In proof-of-concept cellular experiments, an increased cellular internalization of NP-PEG/PS25 and NP-NH2/PS25 compared to the respective bare nanoparticles was observed, as well as a decreased cellular uptake, both in the nuclei and in the cytoplasm, in both NP-PEG/EPC25 and NP-COOH/EPC25 systems with respect to the cationic lipids alone. Moreover, intracellular FRET processes were detected by in vitro cell imaging with confocal microscopy, emphasizing the potentialities of such nanoplatforms in theranostic applications

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

Tandem Dye-Doped Nanoparticles for NIR Imaging via Cerenkov Resonance Energy Transfer

The detection of the Cerenkov radiation (CR) is an emerging preclinical imaging technique which allows monitoring the in vivo distribution of radionuclides. Among its possible advantages, the most interesting is the simplicity and cost of the required instrumentation compared, e.g., to that required for PET scans. On the other hand, one of its main drawbacks is related to the fact that CR, presenting the most intense component in the UV-vis region, has a very low penetration in biological tissues. To address this issue, we present here multifluorophoric silica nanoparticles properly designed to efficiently absorb the CR radiation and to have a quite high fluorescence quantum yield (0.12) at 826 nm. Thanks to a highly efficient series of energy transfer processes, each nanoparticle can convert part of the CR into NIR light, increasing its detection even under 1.0-cm thickness of muscle

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

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. © 2014 The Partner Organisations

Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities

Stefania Biffi,1 Luca Petrizza,2 Chiara Garrovo,1 Enrico Rampazzo,2 Laura Andolfi,3 Pierangela Giustetto,4 Ivaylo Nikolov,5 Gabor Kurdi,5 Miltcho Boyanov Danailov,5 Giorgio Zauli,1 Paola Secchiero,6 Luca Prodi2 1Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 2Department of Chemistry ‘‘G Ciamician’’, University of Bologna, Bologna, 3IOM-CNR TASC Laboratory, Basovizza, Trieste, 4Ephoran – Multi-Imaging Solutions, Bioindustry Park Silvano Fumero, Torino, 5Elettra-Sincrotrone Trieste, Trieste, 6Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy Purpose: The aim of the present study was to develop nanoprobes with theranostic features, including – at the same time – photoacoustic, near-infrared (NIR) optical imaging, and photothermal properties, in a versatile and stable core–shell silica-polyethylene glycol (PEG) nanoparticle architecture. Materials and methods: We synthesized core–shell silica-PEG nanoparticles by a one-pot direct micelles approach. Fluorescence emission and photoacoustic and photothermal properties were obtained at the same time by appropriate doping with triethoxysilane-derivatized cyanine 5.5 (Cy5.5) and cyanine 7 (Cy7) dyes. The performances of these nanoprobes were measured in vitro, using nanoparticle suspensions in phosphate-buffered saline and blood, dedicated phantoms, and after incubation with MDA-MB-231 cells. Results: We obtained core–shell silica-PEG nanoparticles endowed with very high colloidal stability in water and in biological environment, with absorption and fluorescence emission in the NIR field. The presence of Cy5.5 and Cy7 dyes made it possible to reach a more reproducible and higher doping regime, producing fluorescence emission at a single excitation wavelength in two different channels, owing to the energy transfer processes within the nanoparticle. The nanoarchitecture and the presence of both Cy5.5 and Cy7 dyes provided a favorable agreement between fluorescence emission and quenching, to achieve optical imaging and photoacoustic and photothermal properties. Conclusion: We obtained rationally designed nanoparticles with outstanding stability in biological environment. At appropriate doping regimes, the presence of Cy5.5 and Cy7 dyes allowed us to tune fluorescence emission in the NIR for optical imaging and to exploit quenching processes for photoacoustic and photothermal capabilities. These nanostructures are promising in vivo theranostic tools for the near future. Keywords: dye-doped nanoparticles, optical imaging, NIR imaging, photoacoustic imaging, photothermal therapy, PEGylated nanoparticle

Further optimization of plakortin pharmacophore: Structurally simple 4-oxymethyl-1,2-dioxanes with promising antimalarial activity

For the optimization of the plakortin pharmacophore, we recently proposed a straightforward synthesis of 4-carbomethoxy-3-methoxy-1,2-dioxanes as potential antimalarial drug candidates. Herein we report the chemoselective reduction of the 4-carbomethoxy group which has allowed us to prepare in good yields twenty-four new endoperoxides carrying either the hydroxymethyl or the methoxymethyl group on C4 in various stereochemical arrangements with respect to the alkyl groups on C3 and C6 (the endoperoxide carbons). Some of these compounds showed promising in vitro antimalarial activities, both against chloroquine-resistant (CQ-R) and susceptible (CQ-S) strains of Plasmodium falciparum, with IC50 values in the range of 0.5e1.0 mM. Compound 8g showed activity against the CQ-R strain comparable to that of the structurally more demanding plakortin

Further optimization of Plakortin pharmacophore: structurally simple 4-oxymethyl-1,2-dioxanes with promising antimalarial activity

For the optimization of the plakortin pharmacophore, we recently proposed a straightforward synthesis of 4-carbomethoxy-3-methoxy-1,2-dioxanes as potential antimalarial drug candidates. Herein we report the chemoselective reduction of the 4-carbomethoxy group which has allowed us to prepare in good yields twenty-four new endoperoxides carrying either the hydroxymethyl or the methoxymethyl group on C4 in various stereochemical arrangements with respect to the alkyl groups on C3 and C6 (the endoperoxide carbons). Some of these compounds showed promising in vitro antimalarial activities, both against chloroquine-resistant (CQ-R) and susceptible (CQ-S) strains of Plasmodium falciparum, with IC50 values in the range of 0.5-1.0 μM. Compound 8g showed activity against the CQ-R strain comparable to that of the structurally more demanding plakorti