102 results on '"Prodi, Luca"'
Search Results
2. Palladium Complexes of N-Methylcorroles.
- Author
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Pizzoli F, Mita A, Caroleo F, Nardis S, Calice U, Caporale M, Belviso S, Superchi S, Marconi A, Calvaresi M, Capolungo C, Prodi L, Smith KM, Fronczek FR, and Paolesse R
- Abstract
Alkylation of one of the inner-core nitrogen atoms is one possible approach to obtain dianionic corrole ligands, suitable for the coordination of divalent metal ions, such as Pd
II . Inner-core N-methylation can be obtained by treating the corrole with CH3 I, but the reaction conditions should be optimized to limit the formation of the dimethylated derivative. Two regioisomers, the N-21 and the N-22 methyl derivatives are obtained from the reaction, with the first product achieved in a higher amount. Structural characterization of the reaction products evidenced the distortion induced by the introduction of the methyl groups; the N-methylcorroles are chiral compounds, and the enantiomers were separated by chromatography, with their absolute configuration assigned by ECD computation. Palladium insertion was achieved in the case of monosubstituted corroles, but not with the dimethylated macrocycle; X-ray characterization of the complexes showed the distortion of the macrocycles. The Pd complexes do not show luminescence emission, but are able to produce singlet oxygen upon irradiation. The PdII complexes were also inserted in human serum albumin (HSA) and dispersed in water; in this case, the protein protects the corroles from photobleaching, and a switch from the type II to the type I mechanism in reactive oxygen species (ROS) production is observed., (© 2023 Wiley-VCH GmbH.)- Published
- 2023
- Full Text
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3. A modular phage vector platform for targeted photodynamic therapy of Gram-negative bacterial pathogens.
- Author
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Petrosino A, Saporetti R, Starinieri F, Sarti E, Ulfo L, Boselli L, Cantelli A, Morini A, Zadran SK, Zuccheri G, Pasquini Z, Di Giosia M, Prodi L, Pompa PP, Costantini PE, Calvaresi M, and Danielli A
- Abstract
Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very few efforts have been made to combine the advantages of both approaches in a modular, retargetable platform. Here, we foster the M13 bacteriophage as a multifunctional scaffold, enabling the selective photodynamic killing of bacteria. We took advantage of the well-defined molecular biology of M13 to functionalize its capsid with hundreds of photo-activable Rose Bengal sensitizers and contemporarily target this light-triggerable nanobot to specific bacterial species by phage display of peptide targeting moieties fused to the minor coat protein pIII of the phage. Upon light irradiation of the specimen, the targeted killing of diverse Gram(-) pathogens occurred at subnanomolar concentrations of the phage vector. Our findings contribute to the development of antimicrobials based on targeted and triggerable phage-based nanobiotherapeutics., Competing Interests: There are no conflicts to declare., (© 2023 The Author(s).)
- Published
- 2023
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4. Fluorescent sensing of non-steroidal anti-inflammatory drugs naproxen and ketoprofen by dansylated squaramide-based receptors.
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Picci G, Aragoni MC, Arca M, Caltagirone C, Formica M, Fusi V, Giorgi L, Ingargiola F, Lippolis V, Macedi E, Mancini L, Mummolo L, and Prodi L
- Subjects
- Dimethyl Sulfoxide, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Anti-Inflammatory Agents, Non-Steroidal chemistry, Naproxen pharmacology, Naproxen chemistry, Ketoprofen pharmacology, Ketoprofen chemistry
- Abstract
Bis-squaramide receptors L1-L4 bearing a dansyl moiety were synthesised and their potential applications as fluorescent probes towards non steroidal anti-inflammatory drugs naproxen and ketoprofen was investigated. A detailed photophysical characterization in CH
3 CN/DMSO solution (9 : 1 v/v) was conducted and demonstrated that the two macrocyclic receptors L1 and L2 show good sensitivity towards ketoprofen with an ON-OFF fluorescent response, while the two open chain receptors L3 and L4 behave similarly with the three guests considered. DFT theoretical calculations carried out on L2 and L4 as model receptors allowed to propose a possible coordination mode towards the guests. Finally,1 H-NMR spectroscopy in DMSO- d6 /0.5% water solution demonstrated that the four receptors interact with the considered guests via H-bonds.- Published
- 2023
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5. Dissecting the Interactions between Chlorin e6 and Human Serum Albumin.
- Author
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Marconi A, Mattioli EJ, Ingargiola F, Giugliano G, Marforio TD, Prodi L, Di Giosia M, and Calvaresi M
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- Humans, Serum Albumin, Human metabolism, Photosensitizing Agents chemistry, Tissue Distribution, Cell Line, Tumor, Porphyrins chemistry, Chlorophyllides, Photochemotherapy methods
- Abstract
Chlorin e6 (Ce6) is among the most used sensitizers in photodynamic (PDT) and sonodynamic (SDT) therapy; its low solubility in water, however, hampers its clinical exploitation. Ce6 has a strong tendency to aggregate in physiological environments, reducing its performance as a photo/sono-sensitizer, as well as yielding poor pharmacokinetic and pharmacodynamic properties. The interaction of Ce6 with human serum albumin (HSA) (i) governs its biodistribution and (ii) can be used to improve its water solubility by encapsulation. Here, using ensemble docking and microsecond molecular dynamics simulations, we identified the two Ce6 binding pockets in HSA, i.e., the Sudlow I site and the heme binding pocket, providing an atomistic description of the binding. Comparing the photophysical and photosensitizing properties of Ce6@HSA with respect to the same properties regarding the free Ce6, it was observed that (i) a red-shift occurred in both the absorption and emission spectra, (ii) a maintaining of the fluorescence quantum yield and an increase of the excited state lifetime was detected, and (iii) a switch from the type II to the type I mechanism in a reactive oxygen species (ROS) production, upon irradiation, took place.
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- 2023
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6. Interaction between Engineered Pluronic Silica Nanoparticles and Bacterial Biofilms: Elucidating the Role of Nanoparticle Surface Chemistry and EPS Matrix.
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Vitale S, Rampazzo E, Hiebner D, Devlin H, Quinn L, Prodi L, and Casey E
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- Biofilms, Poloxamer, Silicon Dioxide, Extracellular Polymeric Substance Matrix, Nanoparticles
- Abstract
Nanoparticles (NPs) are considered a promising tool in the context of biofilm control. Many studies have shown that different types of NPs can interfere with the bacterial metabolism and cellular membranes, thus making them potential antibacterial agents; however, fundamental understanding is still lacking on the exact mechanisms involved in these actions. The development of NP-based approaches for effective biofilm control also requires a thorough understanding of how the chosen nanoparticles will interact with the biofilm itself, and in particular with the biofilm self-produced extracellular polymeric matrix (EPS). This work aims to provide advances in the understanding of the interaction between engineered fluorescent pluronic silica (PluS) nanoparticles and bacterial biofilms, with a main focus on the role of the EPS matrix in the accumulation and diffusion of the particles in the biofilm. It is demonstrated that particle surface chemistry has a key role in the different lateral distribution and specific affinity to the biofilm matrix components. The results presented in this study contribute to our understanding of biofilm-NP interactions and promote the principle of the rational design of smart nanoparticles as an important tool for antibiofilm technology.
- Published
- 2022
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7. Ultrasensitive PCR-Free detection of whole virus genome by electrochemiluminescence.
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Nikolaou P, Sciuto EL, Zanut A, Petralia S, Valenti G, Paolucci F, Prodi L, and Conoci S
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- Genome, Viral, Hepatitis B virus genetics, Humans, Polymerase Chain Reaction, Biosensing Techniques methods, COVID-19 diagnosis, Communicable Diseases
- Abstract
Detection of nucleic acids is crucial in many medical applications, and in particular for monitoring infectious diseases, as it has become perfectly clear after the pandemic infection of COVID-19. In this context, the development of innovative detection methods based on signal-amplification rather than analyte-amplification represents a significant breakthrough compared to existing PCR-based methodologies, allowing the development of new nucleic acid detection technologies suitable to be integrated in portable and low-cost sensor devices while keeping high sensitivities, thus enabling massive diagnostic screening. In this work, we present a novel molecular sensor for the ultrasensitive PCR-free detection of Hepatitis B Virus (HBV) based on electrochemiluminescence (ECL). Thanks to the combination of surface cooperative hybridization scheme with ECL detection strategy, our novel DNA sensor is able to detect HBV genome - both synthetic and extracted - with the unprecedented limit of detection (LoD) of 0.05 cps μL
-1 for extracted sample, that is even lower than the typical LoD of PCR methodologies. The detection concept presented here for HBV detection is very versatile and can be extended to other pathogens, paving the way for future development of rapid molecular test for infectious diseases, both viral and bacterial, in Point-of-Care (PoC) format., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
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8. Polyamine receptors containing anthracene as fluorescent probes for ketoprofen in H 2 O/EtOH solution.
- Author
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Romano GM, Mummolo L, Savastano M, Paoli P, Rossi P, Prodi L, and Bencini A
- Subjects
- Anthracenes, Carrier Proteins metabolism, Ethanol, Polyamines metabolism, Fluorescent Dyes, Ketoprofen
- Abstract
Triamine receptors containing anthracene units are able to bind and sense ketoprofen via fluorescence enhancement in a H
2 O/EtOH 50 : 50 (Vol : Vol) mixture exploiting their protonation features, which are tuned by the interaction with the analyte.- Published
- 2022
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9. Photoluminescence-Based Techniques for the Detection of Micro- and Nanoplastics.
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Capolungo C, Genovese D, Montalti M, Rampazzo E, Zaccheroni N, and Prodi L
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- Humans, Microplastics, Plastics
- Abstract
The growing numbers related to plastic pollution are impressive, with ca. 70 % of produced plastic (>350 tonnes/year) being indiscriminately wasted in the environment. The most dangerous forms of plastic pollution for biota and human health are micro- and nano-plastics (MNPs), which are ubiquitous and more bioavailable. Their elimination is extremely difficult, but the first challenge is their detection since existing protocols are unsatisfactory for microplastics and mostly absent for nanoplastics. After a discussion of the state of the art for MNPs detection, we specifically revise the techniques based on photoluminescence that represent very promising solutions for this problem. In this context, Nile Red staining is the most used strategy and we show here its pros and limitations, but we also discuss other more recent approaches, such as the use of fluorogenic probes based on perylene-bisimide and on fluorogenic hyaluronan nanogels, with the added values of biocompatibility and water solubility., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
- Published
- 2021
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10. Static quenching upon adduct formation: a treatment without shortcuts and approximations.
- Author
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Genovese D, Cingolani M, Rampazzo E, Prodi L, and Zaccheroni N
- Abstract
Luminescence quenching is a process exploited in transversal applications in science and technology and it has been studied for a long time. The luminescence quenching mechanisms are typically distinguished in dynamic (collisional) and static, which can require different quantitative treatments. This is particularly important - and finds broad and interdisciplinary application - when the static quenching is caused by the formation of an adduct between the luminophore - at the ground state - and the quencher. Due to its nature, this case should be treated starting from the well-known law of mass action although, in specific conditions, general equations can be conveniently reduced to simpler ones. A proper application of simplified equations, though, can be tricky, with frequent oversimplifications taking to severe errors in the interpretation of the photophysical data. This tutorial review aims to (i) identify the precise working conditions for the application of the simplified equations of static quenching and to (ii) provide general equations for broadest versatility and applicability. The latter equations can be used even beyond the sole case of pure quenching, i.e., in the cases of partial quenching and even luminescence turn-on. Finally, we illustrate different applications of the equations via a critical discussion of examples in the field of sensing, supramolecular chemistry and nanotechnology.
- Published
- 2021
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11. Nitroxides as Building Blocks for Nanoantioxidants.
- Author
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Genovese D, Baschieri A, Vona D, Baboi RE, Mollica F, Prodi L, Amorati R, and Zaccheroni N
- Abstract
Nitroxides are an important class of radical trapping antioxidants whose promising biological activities are connected to their ability to scavenge peroxyl (ROO
• ) radicals. We have measured the rate constants of the reaction with ROO• ( kinh ) for a series of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) derivatives as 5.1 × 106 , 1.1 × 106 , 5.4 × 105 , 3.7 × 105 , 1.1 × 105 , 1.9 × 105 , and 5.6 × 104 M-1 s-1 for -H, -OH, -NH2 , -COOH, -NHCOCH3 , -CONH(CH2 )3 CH3 , and ═O substituents in the 4 position, with a good Marcus relationship between log ( kinh ) and E ° for the R2 NO• /R2 NO+ couple. Newly synthesized Pluronic-silica nanoparticles (PluS) having nitroxide moieties covalently bound to the silica surface (PluS-NO) through a TEMPO-CONH-R link and coumarin dyes embedded in the silica core, has kinh = 1.5 × 105 M-1 s-1 . Each PluS-bound nitroxide displays an inhibition duration nearly double that of a structurally related "free" nitroxide. As each PluS-NO particle bears an average of 30 nitroxide units, this yields an overall ≈60-fold larger inhibition of the PluS-NO nanoantioxidant compared to the molecular analogue. The implications of these results for the development of novel nanoantioxidants based on nitroxide derivatives are discussed, such as the choice of the best linkage group and the importance of the regeneration cycle in determining the duration of inhibition.- Published
- 2021
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12. A Selective Ratiometric Fluorescent Probe for No-Wash Detection of PVC Microplastic.
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Caponetti V, Mavridi-Printezi A, Cingolani M, Rampazzo E, Genovese D, Prodi L, Fabbri D, and Montalti M
- Abstract
Microplastics (MP) are micrometric plastic particles present in drinking water, food and the environment that constitute an emerging pollutant and pose a menace to human health. Novel methods for the fast detection of these new contaminants are needed. Fluorescence-based detection exploits the use of specific probes to label the MP particles. This method can be environmentally friendly, low-cost, easily scalable but also very sensitive and specific. Here, we present the synthesis and application of a new probe based on perylene-diimide (PDI), which can be prepared in a few minutes by a one-pot reaction using a conventional microwave oven and can be used for the direct detection of MP in water without any further treatment of the sample. The green fluorescence is strongly quenched in water at neutral pH because of the formation dimers. The ability of the probe to label MP was tested for polyvinyl chloride (PVC), polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP), polystyrene (PS), poly methyl methacrylate (PMMA) and polytetrafluoroethylene (PTFE). The probe showed considerable selectivity to PVC MP, which presented an intense red emission after staining. Interestingly, the fluorescence of the MP after labeling could be detected, under excitation with a blue diode, with a conventional CMOS color camera. Good selectivity was achieved analyzing the red to green fluorescence intensity ratio. UV-Vis absorption, steady-state and time-resolved fluorescence spectroscopy, fluorescence anisotropy, fluorescence wide-field and confocal laser scanning microscopy allowed elucidating the mechanism of the staining in detail.
- Published
- 2021
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13. Core-Shell Pluronic-Organosilica Nanoparticles with Controlled Polarity and Oxygen Permeability.
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De La Encarnacion Bermudez C, Haddadi E, Rampazzo E, Petrizza L, Prodi L, and Genovese D
- Abstract
Nanostructured systems constitute versatile carriers with multiple functions engineered in a nanometric space. Yet, such multimodality often requires adapting the chemistry of the nanostructure to the properties of the hosted functional molecules. Here, we show the preparation of core-shell Pluronic-organosilica "PluOS" nanoparticles with the use of a library of organosilane precursors. The precursors are obtained via a fast and quantitative click reaction, starting from cost-effective reagents such as diamines and an isocyanate silane derivative, and they condensate in building blocks characterized by a balance between hydrophobic and H-bond-rich domains. As nanoscopic probes for local polarity, oxygen permeability, and solvating properties, we use, respectively, solvatochromic, phosphorescent, and excimer-forming dyes covalently linked to the organosilica matrix during synthesis. The results obtained here clearly show that the use of these organosilane precursors allows for finely tuning polarity, oxygen permeability, and solvating properties of the resulting organosilica core, expanding the toolbox for precise engineering of the particle properties.
- Published
- 2021
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14. Exploring the Ability of Luminescent Metal Assemblies to Bind and Sense Anionic or Ionizable Analytes A Ru(phen) 2 bipy-Based Dizinc Complex for Bisphenol A (BPA) Recognition.
- Author
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Conti L, Mummolo L, Romano GM, Giorgi C, Giacomazzo GE, Prodi L, and Bencini A
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- 2,2'-Dipyridyl chemistry, Anions chemistry, Benzhydryl Compounds chemistry, Ligands, Luminescence, Metals chemistry, Molecular Structure, Phenols chemistry, Ruthenium chemistry, Benzhydryl Compounds isolation & purification, Phenols isolation & purification, Water chemistry
- Abstract
The synthesis of a new Ru
II complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2'-bipyridyl unit linked, via methylene bridges in its 4 and 4' positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)2 L ]2+ ) is reported. Protonation and ZnII binding by [Ru(phen)2 L ]2+ have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear ZnII /RuII complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)2 L ]2+ is able to bind BPA in aqueous solution, affording a remarkably stable {Zn2 [Ru(phen)2 L ]BPA(H-2 )}4+ adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two ZnII ions. BPA binding was found to quench the luminescence emission of the RuII (phen)2 bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.- Published
- 2021
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15. Dye-Doped Silica Nanoparticles for Enhanced ECL-Based Immunoassay Analytical Performance.
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Zanut A, Palomba F, Rossi Scota M, Rebeccani S, Marcaccio M, Genovese D, Rampazzo E, Valenti G, Paolucci F, and Prodi L
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- Coloring Agents chemical synthesis, Electrochemical Techniques, Humans, Luminescent Measurements, Molecular Structure, Nanotechnology, Particle Size, Surface Properties, Coloring Agents chemistry, Immunoassay, Nanoparticles chemistry, Organometallic Compounds chemistry, Silicon Dioxide chemistry
- Abstract
The combination of highly sensitive techniques such as electrochemiluminescence (ECL) with nanotechnology sparked new analytical applications, in particular for immunoassay-based detection systems. In this context, nanomaterials, particularly dye-doped silica nanoparticles (DDSNPs) are of high interest, since they can offer several advantages in terms of sensitivity and performance. In this work we synthesized two sets of monodispersed and biotinylated [Ru(bpy)
3 ]2+ -doped silica nanoparticles, named bio-Triton@RuNP and bio-Igepal@RuNP, obtained following the reverse microemulsion method using two different types of nonionic surfactants. Controlling the synthetic procedures, we were able to obtain nanoparticles (NPs) offering highly intense signal, using tri-n-propylamine (TPrA) as coreactant, with bio-Triton@RuNps being more efficient than bio-Igepal@RuNP., (© 2020 Wiley-VCH GmbH.)- Published
- 2020
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16. Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein.
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De Marco R, Rampazzo E, Zhao J, Prodi L, Paolillo M, Picchetti P, Gallo F, Calonghi N, and Gentilucci L
- Abstract
Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro validation of a synthetic mimic of Smac/DIABLO, based on fluorescent polyethylene glycol (PEG)-coated silica-core nanoparticles (NPs) carrying a Smac/DIABLO-derived pro-apoptotic peptide and a tumor-homing integrin peptide ligand. At low μM concentration, the NPs showed significant toxicity towards A549, U373, and HeLa cancer cells and modest toxicity towards other integrin-expressing cells, correlated with integrin-mediated cell uptake and consequent highly increased levels of apoptotic activity, without perturbing cells not expressing the α5 integrin subunit.
- Published
- 2020
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17. Tandem Dye-Doped Nanoparticles for NIR Imaging via Cerenkov Resonance Energy Transfer.
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Genovese D, Petrizza L, Prodi L, Rampazzo E, De Sanctis F, Spinelli AE, Boschi F, and Zaccheroni N
- Abstract
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., (Copyright © 2020 Genovese, Petrizza, Prodi, Rampazzo, De Sanctis, Spinelli, Boschi and Zaccheroni.)
- Published
- 2020
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18. Specific, Surface-Driven, and High-Affinity Interactions of Fluorescent Hyaluronan with PEGylated Nanomaterials.
- Author
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Palomba F, Rampazzo E, Zaccheroni N, Malferrari M, Rapino S, Greco V, Satriano C, Genovese D, and Prodi L
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- Cell Membrane chemistry, Cell Membrane metabolism, Fluorescence, HeLa Cells, Humans, Hyaluronic Acid metabolism, Nanoparticles chemistry, Nanoparticles metabolism, Rhodamines chemistry, Rhodamines metabolism, Silicon Dioxide chemistry, Hyaluronic Acid chemistry, Nanostructures chemistry, Polyethylene Glycols chemistry
- Abstract
Hybrid nanomaterials are a subject of extensive research in nanomedicine, and their clinical application is reasonably envisaged in the near future. However, the fate of nanomaterials in biological environments poses serious limitations to their application; therefore, schemes to monitor them and gain control on their toxicity could be of great help for the development of the field. Here, we propose a probe for PEGylated nanosurfaces based on hyaluronic acid (HA) functionalized with rhodamine B (RB). We show that the high-affinity interaction of this fluorogenic hyaluronan (HA-RB) with nanoparticles exposing PEGylated surfaces results in their sensing, labeling for super-resolution imaging, and synergistic cellular internalization. HA-RB forms nanogels that interact with high affinity-down to the picomolar range-with silica nanoparticles, selectively when their surface is covered by a soft and amphiphilic layer. This surface-driven interaction triggers the enhancement of the luminescence intensity of the dyes, otherwise self-quenched in HA-RB nanogels. The sensitive labeling of specific nanosurfaces also allowed us to obtain their super-resolution imaging via binding-activated localization microscopy (BALM). Finally, we show how this high-affinity interaction activates a synergistic cellular uptake of silica nanoparticles and HA-RB nanogels, followed by a differential fate of the two partner nanomaterials inside cells.
- Published
- 2020
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19. Optimized synthesis of luminescent silica nanoparticles by a direct micelle-assisted method.
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Del Secco B, Ravotto L, Esipova TV, Vinogradov SA, Genovese D, Zaccheroni N, Rampazzo E, and Prodi L
- Abstract
Silica nanoparticles (NPs) are versatile nanomaterials, which are safe with respect to biomedical applications, and therefore are highly investigated. The advantages of NPs include their ease of preparation, inexpensive starting materials and the possibility of functionalization or loading with various doping agents. However, the solubility of the doping agent(s) imposes constraints on the choice of the reaction system and hence limits the range of molecules that can be included in the interior of NPs. To overcome this problem, herein, we improved the current state of the art synthetic strategy based on Pluronic F127 by enabling the synthesis in the presence of large amounts of organic solvents. The new method enables the preparation of nanoparticles doped with large amounts of water-insoluble doping agents. To illustrate the applicability of the technology, we successfully incorporated a range of phosphorescent metalloporphyrins into the interior of NPs. The resulting phosphorescent nanoparticles may exhibit potential for biological oxygen sensing.
- Published
- 2019
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20. PluS Nanoparticles Loaded with Sorafenib: Synthetic Approach and Their Effects on Endothelial Cells.
- Author
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Palomba F, Genovese D, Rampazzo E, Zaccheroni N, Prodi L, and Morbidelli L
- Abstract
Silica nanostructures are widely investigated for theranostic applications since relatively mild and easy synthetic methods allow the fabrication of multicompartment nanoparticles (NPs) and fine modulation of their properties. Here, we report the optimization of a synthetic strategy leading to brightly fluorescent silica NPs with a high loading ability, up to 45 molecules per NP, of Sorafenib, a small molecule acting as an antiangiogenic drug. We demonstrate that these NPs can efficiently release the drug and they are able to inhibit endothelial cell proliferation and migration and network formation. Their lyophilization can endow them with long shelf stability, whereas, once in solution, they show a much slower release compared to analogous micellar systems. Interestingly, Sorafenib released from Pluronic silica NPs completely prevented endothelial cell responses and postreceptor mitogen-activated protein kinase signaling ignited by vascular endothelial growth factor, one of the major players of tumor angiogenesis. Our results indicate that these theranostic systems represent a promising structure for anticancer applications since NPs alone have no cytotoxic effect on cultured endothelial cells, a cell type to which drugs and exogenous material are always in contact once delivered., Competing Interests: The authors declare no competing financial interest.
- Published
- 2019
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21. Engineered Nanostructured Materials for Ofloxacin Delivery.
- Author
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Nuti S, Fernández-Lodeiro J, Del Secco B, Rampazzo E, Rodríguez-González B, Capelo JL, Silva V, Igrejas G, Poeta P, Torres C, Zaccheroni N, Prodi L, Oliveira E, and Lodeiro C
- Abstract
Antibiotic resistance is emerging as a growing worldwide problem and finding solutions to this issue is becoming a new challenge for scientists. As the development of new drugs slowed down, advances in nanotechnology offer great opportunities, with the possibility of designing new systems for carrying, delivery and administration of drugs already in use. Engineered combinations of the synthetic, broad-spectrum antibiotic ofloxacin, rarely studied in this field, with different types of silver, mesoporous silica-based and Pluronic/silica-based nanoparticles have been explored. The nanocarriers as silver core@silica mesoporous (AgMSNPs) and dye-doped silica nanoparticles functionalized with ofloxacin were synthesized and their antibacterial properties studied against S. aureus and E. coli . The best antibacterial results were obtained for the AgMSNPs nanosystem@ofloxacin for the strain S. aureus ATCC 25923, with MIC and MBC values of 5 and 25 μg/mL, proving the efficacy and synergetic effect of the antibiotic and the Ag core of the nanoparticles.
- Published
- 2018
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22. Mapping heterogeneous polarity in multicompartment nanoparticles.
- Author
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Palomba F, Genovese D, Petrizza L, Rampazzo E, Zaccheroni N, and Prodi L
- Abstract
Understanding polarity gradients inside nanomaterials is essential to capture their potential as nanoreactors, catalysts or in drug delivery applications. We propose here a method to obtain detailed, quantitative information on heterogeneous polarity in multicompartment nanostructures. The method is based on a 2-steps procedure, (i) deconvolution of complex emission spectra of two solvatochromic probes followed by (ii) spectrally resolved analysis of FRET between the same solvatochromic dyes. While the first step yields a list of polarities probed in the nanomaterial suspension, the second step correlates the polarities in space. Colocalization of polarities falling within few nanometer radius is obtained via FRET, a process called here nanopolarity mapping. Here, Prodan and Nile Red are tested to map the polarity of a water-dispersable, multicompartment nanostructure, named PluS nanoparticle (NPs). PluS NPs are uniform core-shell nanoparticles with silica cores (diameter ~10 nm) and Pluronic F127 shell (thickness ~7 nm). The probes report on a wide range of nanopolarities among which the dyes efficiently exchange energy via FRET, demonstrating the coexistence of a rich variety of environments within nanometer distance. Their use as a FRET couple highlights the proximity of strongly hydrophobic sites and hydrated layers, and quantitatively accounts for the emission component related to external water, which remains unaffected by FRET processes. This method is general and applicable to map nanopolarity in a large variety of nanomaterials.
- Published
- 2018
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23. Dual-Mode, Anisotropy-Encoded, Ratiometric Fluorescent Nanosensors: Towards Multiplexed Detection.
- Author
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Rampazzo E, Bonacchi S, Juris R, Genovese D, Prodi L, Zaccheroni N, and Montalti M
- Abstract
A nanosensor with dual-mode fluorescence response to pH and an encoded identification signal, was developed by exploiting excitation energy transfer and tailored control of molecular organization in core-shell nanoparticles. Multiple signals were acquired in a simple single-excitation dual-emission channels set-up., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2018
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24. A Fluorescent Sensor Array Based on Heteroatomic Macrocyclic Fluorophores for the Detection of Polluting Species in Natural Water Samples.
- Author
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Lvova L, Caroleo F, Garau A, Lippolis V, Giorgi L, Fusi V, Zaccheroni N, Lombardo M, Prodi L, Di Natale C, and Paolesse R
- Abstract
The development of a novel all-solid-state optical sensor array based on heteroatomic macrocyclic fluorophores (diaza-crown ether, metallocorrole and pyridinophans) for the photographic analysis of liquid media, is presented. The sensitivity of the new optical system toward a number of different species (cations: Li
+ , K+ , Na+ , NH 4 + , Mg2+ , Ca2+ , Co2+ , Cu2+ , Zn2+ , Cd2+ , Pb2+ and anions: NO 2 - , NO 3 - , Cl- , Br- , HCO 3 - ) was evaluated both in single selective sensor mode and in multisensory arrangement. The satisfactory PLS1 regression models between sensor array optical response and analyte concentration were obtained for Cd2+ , Cu2+ , Zn2+ , and NO 2 - ions in all the range of tested concentrations. Among these species the highest attention was focused onto detection of cadmium and nitrite ions, for which the detection limits, DL, estimated by 3σ method were found 0.0013 mg/L and 0.21 mg/L respectively, and these values are lower than the corresponding WHO guideline values of 0.003 mg/L (Cd2+ ) and 2 mg/L ( NO 2 - ). The suitability of the developed sensors implemented with familiar devices for signal acquisition (Light Emitting Diode, LED, as light source and a digital camera as a signal detector), and chemometric methods for data treatment to perform fast and low-cost monitoring of species under interest, in real samples of environmental importance, is demonstrated.- Published
- 2018
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25. Silicon(IV) Corroles.
- Author
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Pomarico G, Monti D, Bischetti M, Savoldelli A, Fronczek FR, Smith KM, Genovese D, Prodi L, and Paolesse R
- Abstract
Silicon complexes of corrole were obtained for the first time by reaction of the free-base corrole with hexachlorodisilane. The peripheral substituents of corrole strongly influence the nature of the reaction products: β-octaalkyl corrole was mainly isolated as the μ-oxo dimer, while a hydroxo complex was obtained in the case of 5,10,15-tris-(pentafluorophenyl)corrole. In the case of meso-tritolyl corrole, a mixture of monomer/μ-oxo dimer was obtained. The silicon corrole complexes are more stable toward hydrolysis than the corresponding porphyrin derivatives and are endowed with brilliant luminescence properties. The high affinity of silicon for fluoride ion allowed investigation of the ability of an Si corrole to serve as a sensor for F
- detection. The strong color variation due to the interaction with the halide ion makes the Si corrole an interesting material for the naked-eye detection of inorganic fluoride., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2018
- Full Text
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26. Non-enzymatic portable optical sensors for microcystin-LR.
- Author
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Lvova L, Guanais Gonçalves C, Prodi L, Lombardo M, Zaccheroni N, Viaggiu E, Congestri R, Guzzella L, Pozzoni F, Di Natale C, and Paolesse R
- Subjects
- Marine Toxins, Molecular Structure, Crown Ethers chemistry, Fluorometry, Microcystins analysis, Optical Phenomena
- Abstract
We present here the development of an all-solid-state optical sensor based on phenyl-substituted diaza-18-crown-6 hydroxyquinoline (DCHQ-Ph) for the indirect selective detection of microcystin-LR (MC-LR), reaching a very low detection limit of 0.05 μg L
-1 , well below the World Health Organisation (WHO) guideline value (1 μg L-1 ) in potable water. We demonstrate the potential applicability of the developed method in fast and low-cost water toxicity estimation.- Published
- 2018
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27. NIR-fluorescent dye doped silica nanoparticles for in vivo imaging, sensing and theranostic.
- Author
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Rampazzo E, Genovese D, Palomba F, Prodi L, and Zaccheroni N
- Subjects
- Animals, Drug Carriers chemistry, Emulsions chemistry, Humans, Micelles, Spectroscopy, Near-Infrared, Theranostic Nanomedicine, Fluorescent Dyes chemistry, Nanoparticles chemistry, Silicon Dioxide chemistry
- Abstract
The development of nanostructures devoted to in vivo imaging and theranostic applications is one of the frontier fields of research worldwide. In this context, silica nanoparticles (SiO
2 -NPs) offer unquestionable positive properties: silica is intrinsically non-toxic, several versatile and accessible synthetic methods are available and many variations are possible, both in terms of porosity and functionalization for delivery and targeting purposes, respectively. Moreover, the accumulation of several dyes within a single nanostructure offers remarkable possibilities to produce very bright and photostable luminescent nanosystems. Advancements in imaging technology, bioassay, fluorescent molecular probes have boosted the efforts to develop dye doped fluorescent SiO2 -NPs, but despite this, only a quite limited set of systems are applicable in vivo. Herein we discuss selected examples that appeared in the literature between 2013-17, with imaging capabilities in vivo and characterized by a significant near infrared (NIR) fluorescence emission. We present here very promising strategies to develop SiO2 -NPs for diagnostic and therapeutic applications-some of which are already in clinical trials-and the possibility to develop bio-erodable SiO2 -NPs. We are convinced that all these findings will be the basis for the spread of SiO2 -NPs into clinical use in the near future.- Published
- 2018
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28. Synthesis of a highly Mg 2+ -selective fluorescent probe and its application to quantifying and imaging total intracellular magnesium.
- Author
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Sargenti A, Farruggia G, Zaccheroni N, Marraccini C, Sgarzi M, Cappadone C, Malucelli E, Procopio A, Prodi L, Lombardo M, and Iotti S
- Subjects
- Cell Line, Tumor, Fluorescent Dyes chemistry, Humans, Hydroxyquinolines chemical synthesis, Hydroxyquinolines chemistry, Hydroxyquinolines metabolism, Chemistry Techniques, Synthetic methods, Fluorescent Dyes chemical synthesis, Fluorescent Dyes metabolism, Intracellular Space metabolism, Magnesium metabolism, Microscopy, Fluorescence
- Abstract
Magnesium plays a crucial role in many physiological functions and pathological states. Therefore, the evolution of specific and sensitive tools capable of detecting and quantifying this element in cells is a very desirable goal in biological and biomedical research. We developed a Mg
2+ -selective fluorescent dye that can be used to selectively detect and quantify the total magnesium pool in a number of cells that is two orders of magnitude smaller than that required by flame atomic absorption spectroscopy (F-AAS), the reference analytical method for the assessment of cellular total metal content. This protocol reports itemized steps for the synthesis of the fluorescent dye based on diaza-18-crown-6-hydroxyquinoline (DCHQ5). We also describe its application in the quantification of total intracellular magnesium in mammalian cells and the detection of this ion in vivo by confocal microscopy. The use of in vivo confocal microscopy enables the quantification of magnesium in different cellular compartments. As an example of the sensitivity of DCHQ5, we studied the involvement of Mg2+ in multidrug resistance in human colon adenocarcinoma cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin, and found that the concentration was higher in LoVo-R cells. The time frame for DCHQ5 synthesis is 1-2 d, whereas the use of this dye for total intracellular magnesium quantification takes 2.5 h and for ion bioimaging it takes 1-2 h.- Published
- 2017
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29. Cubosomes for in vivo fluorescence lifetime imaging.
- Author
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Biffi S, Andolfi L, Caltagirone C, Garrovo C, Falchi AM, Lippolis V, Lorenzon A, Macor P, Meli V, Monduzzi M, Obiols-Rabasa M, Petrizza L, Prodi L, Rosa A, Schmidt J, Talmon Y, and Murgia S
- Subjects
- Animals, Carbocyanines pharmacokinetics, Carbocyanines pharmacology, Cell Survival drug effects, Drug Compounding methods, Erythrocytes drug effects, Female, Fluorescent Dyes pharmacokinetics, Fluorescent Dyes pharmacology, Glycerides chemistry, Humans, Injections, Intravenous, Liposomes chemical synthesis, Liver drug effects, Liver metabolism, Liver ultrastructure, Mice, Mice, Inbred BALB C, NIH 3T3 Cells, Nanoparticles administration & dosage, Particle Size, Time-Lapse Imaging, Carbocyanines chemistry, Fluorescent Dyes chemistry, Liposomes pharmacokinetics, Nanoparticles chemistry, Optical Imaging methods, Spectroscopy, Near-Infrared methods
- Abstract
Herein we provided the first proof of principle for in vivo fluorescence optical imaging application using monoolein-based cubosomes in a healthy mouse animal model. This formulation, administered at a non-cytotoxic concentration, was capable of providing both exogenous contrast for NIR fluorescence imaging with very high efficiency and chemospecific information upon lifetime analysis. Time-resolved measurements of fluorescence after the intravenous injection of cubosomes revealed that the dye rapidly accumulated mainly in the liver, while lifetimes profiles obtained in vivo allowed for discriminating between free dye or dye embedded within the cubosome nanostructure after injection.
- Published
- 2017
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30. A Highly Emissive Water-Soluble Phosphorus Corrole.
- Author
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Naitana ML, Nardis S, Pomarico G, Raggio M, Caroleo F, Cicero DO, Lentini S, Prodi L, Genovese D, Mitta S, Sgarlata A, Fanfoni M, Persichetti L, and Paolesse R
- Abstract
The synthesis, spectroscopic, and optical properties of the water-soluble phosphorus complex of a 2-sulfonato-10-(4-sulfonatophenyl)-5,15-dimesitylcorrole have been investigated. The compound was prepared by adopting a novel strategy for the corrole sulfonation, leading to the regioselective isomer in an almost quantitative yield. The phosphorus coordination has a key role in determining the corrole substitution pattern, limiting the formation of poly-substituted species, which affected the reaction of the corrole free base. The resulting complex shows excellent optical properties in terms of emission quantum yield, also in polar protic solvents, including water.
31 P NMR spectroscopy in CD3 OD indicates that the P sulfonate complex has been isolated in a hexacoordinated geometry with two different ligands (L1=-OH, L2=-OCH3 ), and it is prone to axial ligand exchange with methanol, with no evidence of intermediate pentacoordinated species. The morphological characterization of thin layers of the P corrole deposited onto an Au(111) surface showed that the addition of an intermediate layer of reduced graphene oxide allows for a better control of corrole aggregation, inducing also transformation of the Au(111) reconstructed surface., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2017
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31. Variable Doping Induces Mechanism Swapping in Electrogenerated Chemiluminescence of Ru(bpy) 3 2+ Core-Shell Silica Nanoparticles.
- Author
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Valenti G, Rampazzo E, Bonacchi S, Petrizza L, Marcaccio M, Montalti M, Prodi L, and Paolucci F
- Abstract
The impact of nanotechnology on analytical science is hardly overlooked. In the search for ever-increasing sensitivity in biomedical sensors, nanoparticles have been playing a unique role as, for instance, ultrabright labels, and unravelling the intimate mechanisms which govern their functioning is mandatory for the design of ultrasentitive devices. Herein, we investigated the mechanism of electrogenerated chemiluminescence (ECL) in a family of core-shell silica-PEG nanoparticles (DDSNs), variously doped with a Ru(bpy)
3 2+ triethoxysilane derivative, and displaying homogeneous morphological, hydrodynamic, and photophysical properties. ECL experiments, performed in the presence of 2-(dibutylamino)ethanol (DBAE) as coreactant, showed two parallel mechanisms of ECL generation: one mechanism (I) which involves exclusively the radicals deriving from the coreactant oxidation and a second one (II) involving also the direct anodic oxidation of the Ru(II) moieties. The latter mechanism includes electron (hole) hopping between neighboring redox centers as evidenced in our previous studies and supported by a theoretical model we have recently proposed. Quite unexpectedly, however, we found that the efficiency of the two mechanisms varies in opposite directions within the DDSNs series, with mechanism I or mechanism II prevailing at low and high doping levels, respectively. Since mechanism II has an intrinsically lower efficiency, the ECL emission intensity was also found to grow linearly with doping only at relatively low doping levels while it deviates negatively at higher ones. As the ζ-potential of DDSNs increases with the doping level from negative to slightly positive values, as a likely consequence of the accumulating cationic charge within the silica core, we attributed the observed change in the ECL generation mechanism along the DDSN series to a modulation of the electrostatic and hydrophobic/hydrophilic interactions between the DDSNs and the radical cationic species involved in the ECL generation. The results we report therefore show that the ECL intensity of a nanosized system cannot be merely incremented acting on doping, since other parameters come into play. We think that these results could serve as valuable indications to design more efficient ECL nano- and microsized labels for ultrasensitive bioanalysis.- Published
- 2016
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32. Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities.
- Author
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Biffi S, Petrizza L, Garrovo C, Rampazzo E, Andolfi L, Giustetto P, Nikolov I, Kurdi G, Danailov MB, Zauli G, Secchiero P, and Prodi L
- Subjects
- Benzothiazoles metabolism, Breast Neoplasms diagnostic imaging, Carbocyanines metabolism, Coloring Agents metabolism, Female, Fluorescence, Humans, Hyperthermia, Induced methods, Micelles, Nanostructures chemistry, Optical Imaging methods, Phototherapy, Tumor Cells, Cultured, Breast Neoplasms pathology, Fluorescent Dyes chemistry, Multimodal Imaging methods, Nanoparticles chemistry, Photoacoustic Techniques methods, Polyethylene Glycols chemistry, Silicon Dioxide chemistry
- Abstract
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.
- Published
- 2016
- Full Text
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33. Reversal of the glycolytic phenotype of primary effusion lymphoma cells by combined targeting of cellular metabolism and PI3K/Akt/ mTOR signaling.
- Author
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Mediani L, Gibellini F, Bertacchini J, Frasson C, Bosco R, Accordi B, Basso G, Bonora M, Calabrò ML, Mattiolo A, Sgarbi G, Baracca A, Pinton P, Riva G, Rampazzo E, Petrizza L, Prodi L, Milani D, Luppi M, Potenza L, De Pol A, Cocco L, Capitani S, and Marmiroli S
- Subjects
- Apoptosis drug effects, Blotting, Western, Cell Proliferation drug effects, Cells, Cultured, Coculture Techniques, Deoxyglucose pharmacology, Epithelium drug effects, Epithelium metabolism, Flow Cytometry, Humans, Lymphoma, Primary Effusion drug therapy, Lymphoma, Primary Effusion pathology, Phenotype, Phosphatidylinositol 3-Kinases metabolism, Protein Array Analysis, Proto-Oncogene Proteins c-akt metabolism, Pyridones pharmacology, Pyrimidines pharmacology, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Glycolysis drug effects, Lymphoma, Primary Effusion metabolism, Phosphoinositide-3 Kinase Inhibitors, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-akt antagonists & inhibitors, TOR Serine-Threonine Kinases antagonists & inhibitors
- Abstract
PEL is a B-cell non-Hodgkin lymphoma, occurring predominantly as a lymphomatous effusion in body cavities, characterized by aggressive clinical course, with no standard therapy. Based on previous reports that PEL cells display a Warburg phenotype, we hypothesized that the highly hypoxic environment in which they grow in vivo makes them more reliant on glycolysis, and more vulnerable to drugs targeting this pathway. We established here that indeed PEL cells in hypoxia are more sensitive to glycolysis inhibition. Furthermore, since PI3K/Akt/mTOR has been proposed as a drug target in PEL, we ascertained that pathway-specific inhibitors, namely the dual PI3K and mTOR inhibitor, PF-04691502, and the Akt inhibitor, Akti 1/2, display improved cytotoxicity to PEL cells in hypoxic conditions. Unexpectedly, we found that these drugs reduce lactate production/extracellular acidification rate, and, in combination with the glycolysis inhibitor 2-deoxyglucose (2-DG), they shift PEL cells metabolism from aerobic glycolysis towards oxidative respiration. Moreover, the associations possess strong synergistic cytotoxicity towards PEL cells, and thus may reduce adverse reaction in vivo, while displaying very low toxicity to normal lymphocytes. Finally, we showed that the association of 2-DG and PF-04691502 maintains its cytotoxic and proapoptotic effect also in PEL cells co-cultured with human primary mesothelial cells, a condition known to mimic the in vivo environment and to exert a protective and pro-survival action. All together, these results provide a compelling rationale for the clinical development of new therapies for the treatment of PEL, based on combined targeting of glycolytic metabolism and constitutively activated signaling pathways.
- Published
- 2016
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34. Luminescent Silica Nanoparticles Featuring Collective Processes for Optical Imaging.
- Author
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Rampazzo E, Prodi L, Petrizza L, and Zaccheroni N
- Subjects
- Luminescence, Spectroscopy, Near-Infrared, Nanoparticles chemistry, Silicon Dioxide chemistry
- Abstract
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.
- Published
- 2016
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- View/download PDF
35. Exploiting Fast Exciton Diffusion in Dye-Doped Polymer Nanoparticles to Engineer Efficient Photoswitching.
- Author
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Trofymchuk K, Prodi L, Reisch A, Mély Y, Altenhöner K, Mattay J, and Klymchenko AS
- Subjects
- Diffusion, Fluorescence Resonance Energy Transfer, Hydrophobic and Hydrophilic Interactions, Polylactic Acid-Polyglycolic Acid Copolymer, Rhodamines chemistry, Tetraphenylborate chemistry, Fluorescent Dyes chemistry, Lactic Acid chemistry, Nanoparticles chemistry, Polyglycolic Acid chemistry
- Abstract
Photoswitching of bright fluorescent nanoparticles opens new possibilities for bioimaging with superior temporal and spatial resolution. However, efficient photoswitching of nanoparticles is hard to achieve using Förster resonance energy transfer (FRET) to a photochromic dye, because the particle size is usually larger than the Förster radius. Here, we propose to exploit the exciton diffusion within the FRET donor dyes to boost photoswitching efficiency in dye-doped polymer nanoparticles. To this end, we utilized bulky hydrophobic counterions that prevent self-quenching and favor communication of octadecyl rhodamine B dyes inside a polymer matrix of poly(D,L-lactide-co-glycolide). Among tested counterions, only perfluorinated tetraphenylborate that favors the exciton diffusion enables high photoswitching efficiency (on/off ratio ∼20). The switching improves with donor dye loading and requires only 0.1-0.3 wt % of a diphenylethene photochromic dye. Our nanoparticles were validated both in solution and at the single-particle level. The proposed concept paves the way to new efficient photoswitchable nanomaterials.
- Published
- 2015
- Full Text
- View/download PDF
36. Applications of nanoparticles in cancer medicine and beyond: optical and multimodal in vivo imaging, tissue targeting and drug delivery.
- Author
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Biffi S, Voltan R, Rampazzo E, Prodi L, Zauli G, and Secchiero P
- Subjects
- Animals, Humans, Nanoparticles therapeutic use, Neoplasms drug therapy, Drug Delivery Systems, Medical Oncology, Multimodal Imaging, Optical Imaging
- Abstract
Introduction: Nanotechnology has opened up the way to the engineering of new organized materials endowed with improved performances. In the past decade, engineered nanoparticles (NPs) have been progressively implemented by exploiting synthetic strategies that yield complex materials capable of performing functions with applications also in medicine. Indeed, in the field of 'nanomedicine' it has been explored the possibility to design multifunctional nanosystems, characterized by high analytical performances and stability, low toxicity and specificity towards a given cell target., Area Covered: In this review article, we summarize the advances in the engineering of NPs for biomedical applications, from optical imaging (OI) to multimodal OI and targeted drug delivery. For this purpose, we will provide some examples of how investigations in nanomedicine can support preclinical and clinical research generating innovative diagnostic and therapeutic strategies in oncology., Expert Opinion: The progressive breakthroughs in nanomedicine have supported the development of multifunctional and multimodal NPs. In particular, NPs are significantly impacting the diagnostic and therapeutic strategies since they allow the development of: NP-based OI probes containing more than one modality-specific contrast agent; surface functionalized NPs for specific 'molecular recognition'. Therefore, the design and characterization of innovative NP-based systems/devices have great applicative potential into the medical field.
- Published
- 2015
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37. An electrochemiluminescence-supramolecular approach to sarcosine detection for early diagnosis of prostate cancer.
- Author
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Valenti G, Rampazzo E, Biavardi E, Villani E, Fracasso G, Marcaccio M, Bertani F, Ramarli D, Dalcanale E, Paolucci F, and Prodi L
- Subjects
- Early Detection of Cancer economics, Humans, Limit of Detection, Luminescence, Male, Microspheres, Early Detection of Cancer methods, Electrochemical Techniques, Prostatic Neoplasms diagnosis, Sarcosine urine, Urinalysis methods
- Abstract
Monitoring Prostate Cancer (PCa) biomarkers is an efficient way to diagnosis this disease early, since it improves the therapeutic success rate and suppresses PCa patient mortality: for this reason a powerful analytical technique such as electrochemiluminescence (ECL) is already used for this application, but its widespread usability is still hampered by the high cost of commercial ECL equipment. We describe an innovative approach for the selective and sensitive detection of the PCa biomarker sarcosine, obtained by a synergistic ECL-supramolecular approach, in which the free base form of sarcosine acts as co-reagent in a Ru(bpy)3(2+)-ECL process. We used magnetic micro-beads decorated with a supramolecular tetraphosphonate cavitand (Tiiii) for the selective capture of sarcosine hydrochloride in a complex matrix like urine. Sarcosine determination was then obtained with ECL measurements thanks to the complexation properties of Tiiii, with a protocol involving simple pH changes - to drive the capture-release process of sarcosine from the receptor - and magnetic micro-bead technology. With this approach we were able to measure sarcosine in the μM to mM window, a concentration range that encompasses the diagnostic urinary value of sarcosine in healthy subjects and PCa patients, respectively. These results indicate how this ECL-supramolecular approach is extremely promising for the detection of sarcosine and for PCa diagnosis and monitoring, and for the development of portable and more affordable devices.
- Published
- 2015
- Full Text
- View/download PDF
38. Luminescence sensing and imaging: general discussion.
- Author
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Ceroni P, Pikramenou Z, Prodi L, Pan Q, Adams D, Weinstein J, Lewis F, Bohne C, Vlcek A, Bassani DM, de Silva AP, Moucheron C, Nocera D, Díaz-Moscoso A, Padilla M, Lemon C, Campagna S, Bradberry S, Galoppini E, Plötz PA, Kelly JM, Rohacova J, Harriman A, Keane P, Gust D, Vos J, Mauro M, De Cola L, Sivaraman SK, Lemercier G, Osborne S, and Monti F
- Published
- 2015
- Full Text
- View/download PDF
39. A fluorescent ratiometric nanosized system for the determination of Pd(II) in water.
- Author
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Arca M, Caltagirone C, De Filippo G, Formica M, Fusi V, Giorgi L, Lippolis V, Prodi L, Rampazzo E, Scorciapino MA, Sgarzi M, and Zaccheroni N
- Abstract
The fluorescent ligand (L) based on the N2S2 pyridinophane macrocycle and the 7-nitrobenzo[1,2,5]oxadiazole (NBD) fluorogenic fragment has been synthesized to coordinate Pd(II) ions. Loaded on dye-doped silica nanoparticles, L can be used as a ratiometric fluorescent chemosensor for Pd(II) in water with high selectivity toward other metal ions including the platinum group ones.
- Published
- 2014
- Full Text
- View/download PDF
40. Cancer-cell-targeted theranostic cubosomes.
- Author
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Caltagirone C, Falchi AM, Lampis S, Lippolis V, Meli V, Monduzzi M, Prodi L, Schmidt J, Sgarzi M, Talmon Y, Bizzarri R, and Murgia S
- Subjects
- Cryoelectron Microscopy, Drug Delivery Systems, Fluorescent Dyes chemistry, Folic Acid chemistry, HeLa Cells, Humans, Light, Magnetic Resonance Spectroscopy, Microscopy, Confocal, Nanomedicine methods, Nanoparticles chemistry, Particle Size, Photochemistry methods, Poloxamer chemistry, Scattering, Small Angle, X-Ray Diffraction, Antineoplastic Agents administration & dosage, Neoplasms drug therapy, Neoplasms metabolism
- Abstract
This work was devoted to the development of a new type of lipid-based (cubosome) theranostic nanoparticle able to simultaneously host camptothecin, a potent anticancer drug, and a squarain-based NIR-emitting fluorescent probe. Furthermore, to confer targeting abilities on these nanoparticles, they were dispersed using mixtures of Pluronic F108 and folate-conjugated Pluronic F108 in appropriate ratios. The physicochemical characterization, performed via SAXS, DLS, and cryo-TEM techniques, proved that aqueous dispersions of such cubosomes can be effectively prepared, while the photophysical characterization demonstrated that these nanoparticles may be used for in vivo imaging purposes. The superior ability of these innovative nanoparticles in targeting cancer cells was emphasized by investigating the lipid droplet alterations induced in HeLa cells upon exposure to targeted and nontargeted cubosomes.
- Published
- 2014
- Full Text
- View/download PDF
41. Energy transfer processes in dye-doped nanostructures yield cooperative and versatile fluorescent probes.
- Author
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Genovese D, Rampazzo E, Bonacchi S, Montalti M, Zaccheroni N, and Prodi L
- Subjects
- Fluorescence Resonance Energy Transfer, Nanomedicine, Poloxamer chemistry, Silicon Dioxide chemistry, Fluorescent Dyes chemistry, Nanoparticles chemistry
- Abstract
Fast and efficient energy transfer among dyes confined in nanocontainers provides the basis of outstanding functionalities in new-generation luminescent probes. This feature article provides an overview of recent research achievements on luminescent Pluronic-Silica NanoParticles (PluS NPs), a class of extremely monodisperse core-shell nanoparticles whose design can be easily tuned to match specific needs for diverse applications based on luminescence, and that have already been successfully tested in in vivo imaging. An outline of their outstanding properties, such as tuneability, bright and photoswitchable fluorescence and electrochemiluminescence, will be supported by a critical discussion of our recent works in this field. Furthermore, novel data and simulations will be presented to (i) thoroughly examine common issues arising from the inclusion of multiple dyes in a small silica core, and (ii) show the emergence of a cooperative behaviour among embedded dyes. Such cooperative behaviour provides a handle for fine control of brightness, emission colour and self-quenching phenomena in PluS NPs, leading to significantly enhanced signal to noise ratios.
- Published
- 2014
- Full Text
- View/download PDF
42. A novel fluorescent chemosensor allows the assessment of intracellular total magnesium in small samples.
- Author
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Sargenti A, Farruggia G, Malucelli E, Cappadone C, Merolle L, Marraccini C, Andreani G, Prodi L, Zaccheroni N, Sgarzi M, Trombini C, Lombardo M, and Iotti S
- Subjects
- Biosensing Techniques methods, Flow Cytometry methods, HL-60 Cells, HT29 Cells, Humans, Biosensing Techniques trends, Fluorescent Dyes chemistry, Intracellular Fluid chemistry, Magnesium analysis
- Abstract
The present study investigated the analytical capabilities of a new fluorescent chemosensor, named DCHQ5, a phenyl derivative belonging to the family of diaza-crown-hydroxyquinolines, for the quantitative assessment of total intracellular Mg content. The results obtained were compared to the analytical performances of DCHQ1 - the parent probe of the series which so far was the only suitable species for the quantitative assessment of the intracellular total magnesium and showed comparable results to atomic absorption spectroscopy. Different protocols were tested in several cell lines both by flow cytometry and by steady state fluorescence spectroscopy assays. The results obtained support the possibility to use DCHQ5 to accurately quantify the intracellular total Mg in much smaller samples than DCHQ1, also displaying an increased stable intracellular staining. These features, combined with the high fluorescence enhancement upon cation binding, and the possibility to be excited both in the UV and visible region, make DCHQ5 a valuable and versatile analytical tool for Mg assessment in biological samples.
- Published
- 2014
- Full Text
- View/download PDF
43. C60@Lysozyme: direct observation by nuclear magnetic resonance of a 1:1 fullerene protein adduct.
- Author
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Calvaresi M, Arnesano F, Bonacchi S, Bottoni A, Calò V, Conte S, Falini G, Fermani S, Losacco M, Montalti M, Natile G, Prodi L, Sparla F, and Zerbetto F
- Subjects
- Chromatography, Gel, Fluorescence, Spectrophotometry, Ultraviolet, Fullerenes chemistry, Magnetic Resonance Spectroscopy methods, Muramidase chemistry
- Abstract
Integrating carbon nanoparticles (CNPs) with proteins to form hybrid functional assemblies is an innovative research area with great promise for medical, nanotechnology, and materials science. The comprehension of CNP-protein interactions requires the still-missing identification and characterization of the 'binding pocket' for the CNPs. Here, using Lysozyme and C60 as model systems and NMR chemical shift perturbation analysis, a protein-CNP binding pocket is identified unambiguously in solution and the effect of the binding, at the level of the single amino acid, is characterized by a variety of experimental and computational approaches. Lysozyme forms a stoichiometric 1:1 adduct with C60 that is dispersed monomolecularly in water. Lysozyme maintains its tridimensional structure upon interaction with C60 and only a few identified residues are perturbed. The C60 recognition is highly specific and localized in a well-defined pocket.
- Published
- 2014
- Full Text
- View/download PDF
44. A quest for supramolecular gelators: silver(I) complexes with quinoline-urea derivatives.
- Author
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Braga D, d'Agostino S, D'Amen E, Grepioni F, Genovese D, Prodi L, and Sgarzi M
- Subjects
- Crystallography, X-Ray, Models, Molecular, Coordination Complexes chemistry, Gels chemistry, Quinolines chemistry, Silver chemistry, Urea analogs & derivatives
- Abstract
The quinoline urea derivatives 1,3-di(quinolin-5-yl)urea (DQ5U), 1-phenyl-3-(quinolin-6-yl)urea (PQ6U), 1-(isoquinolin-5-yl)-3-phenylurea (PiQ5U) and 1-phenyl-3-(3,5-bis(pyrid-2-yl)-1,2,4-triazol-4-yl)urea (PPT4U) have been synthesised and structurally characterized by powder and single crystal X-ray diffraction. Their gelator behaviour in the formation of Ag-complexes has been explored. Compound DQ5U proved capable of gelating the mixed solvent EtOH-DMF 1 : 2 (v/v) when mixed with 1 equivalent of AgNO3. In the case of PQ6U, two polymorphic forms of the complex [Ag(PQ6U)2]NO3, plus the solvated form [Ag(PQ6U)2]NO3·CH3CN, were crystallized. Photophysical characterization of the ligands has been conducted in solution, while fluorescence microscopy has been used to examine the microstructure and photophysical properties of the gels formed by PQ5U and DQ5U with AgNO3.
- Published
- 2013
- Full Text
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45. Surface chemistry architecture of silica nanoparticles determine the efficiency of in vivo fluorescence lymph node mapping.
- Author
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Helle M, Rampazzo E, Monchanin M, Marchal F, Guillemin F, Bonacchi S, Salis F, Prodi L, and Bezdetnaya L
- Subjects
- Animals, Female, Mice, Mice, Inbred BALB C, Microscopy, Electron, Transmission, Surface Properties, Tissue Distribution, Fluorescent Dyes chemistry, Nanoparticles, Sentinel Lymph Node Biopsy methods, Silicon Dioxide chemistry
- Abstract
Near-infrared (NIR) imaging of the lymphatic system offers a sensitive, versatile, and accurate lymph node mapping to locate the first, potentially metastatic, draining nodes in the operating room. Many luminescent nanoprobes have received great attention in this field, and the design of nontoxic and bright nanosystems is of crucial importance. Fluorescent NIR-emitting dye doped silica nanoparticles represent valuable platforms to fulfill these scopes, providing sufficient brightness, resistance to photobleaching, and hydrophilic nontoxic materials. Here, we synthesized these highly stable core-shell nanoparticles with a programmable surface charge positioning and determined the effect of these physicochemical properties on their in vivo behavior. In addition, we characterized their fluorescence kinetic profile in the right axillary lymph node (RALN) mapping. We found that nanoparticles with negative charges hidden by a PEG shell are more appropriate than those with external negative charges in the mapping of lymph nodes. We also demonstrated the efficient excretion of these nanostructures by the hepatobiliary route and their nontoxicity in mice up to 3 months postinjection. These results indicate the potential future development of these fluorescent nanosystems for LN mapping.
- Published
- 2013
- Full Text
- View/download PDF
46. Multimodal use of new coumarin-based fluorescent chemosensors: towards highly selective optical sensors for Hg(2+) probing.
- Author
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Bazzicalupi C, Caltagirone C, Cao Z, Chen Q, Di Natale C, Garau A, Lippolis V, Lvova L, Liu H, Lundström I, Mostallino MC, Nieddu M, Paolesse R, Prodi L, Sgarzi M, and Zaccheroni N
- Subjects
- Animals, COS Cells, Chlorocebus aethiops, Ions chemistry, Microscopy, Confocal, Polyethylene Glycols chemistry, Polyvinyl Chloride chemistry, Quantum Theory, Water chemistry, Coumarins chemistry, Fluorescent Dyes chemistry, Mercury analysis, Nanoparticles chemistry, Spectrometry, Fluorescence
- Abstract
Despite several types of fluorescent sensing molecules have been proposed and examined to signal Hg(2+) ion binding, the development of fluorescence-based devices for in-field Hg(2+) detection and screening in environmental and industrial samples is still a challenging task. Herein, we report the synthesis and characterization of three new coumarin-based fluorescent chemosensors featuring mixed thia/aza macrocyclic framework as receptors units, that is, ligands L1-L3. These probes revealed an OFF-ON selective response to the presence of Hg(2+) ions in MeCN/H2 O 4:1 (v/v), which allowed imaging of this metal ion in Cos-7 cells in vitro. Once included in silica core-polyethylene glycol (PEG) shell nanoparticles or supported on polyvinyl chloride (PVC)-based polymeric membranes, ligands L1-L3 can also selectively sense Hg(2+) ions in pure water. In particular we have developed an optical sensing array tacking advantage of the fluorescent properties of ligand L3 and based on the computer screen photo assisted technique (CSPT). In the device ligand L3 is dispersed into PVC membranes and it quantitatively responds to Hg(2+) ions in natural water samples., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
- Full Text
- View/download PDF
47. β-Pyrazino-fused tetrarylporphyrins.
- Author
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Mandoj F, Nardis S, Pudi R, Lvova L, Fronczek FR, Smith KM, Prodi L, Genovese D, and Paolesse R
- Abstract
A novel method for the preparation of β-fused porphyrin dyads was developed that exploits a one-pot reaction of 2,3-diaminoporphyrins with diethyl oxalate. This approach provides good yields of the zinc β-fused dyad and the corresponding free-base, opening the way for preparation of several metal derivatives to permit modulation of optoelectronic characteristics for commercial applications.
- Published
- 2013
- Full Text
- View/download PDF
48. Proper design of silica nanoparticles combines high brightness, lack of cytotoxicity and efficient cell endocytosis.
- Author
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Rampazzo E, Voltan R, Petrizza L, Zaccheroni N, Prodi L, Casciano F, Zauli G, and Secchiero P
- Subjects
- Animals, Cell Line, Endocytosis drug effects, Flow Cytometry, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, SCID, Microscopy, Fluorescence, Nanoparticles toxicity, Neoplastic Cells, Circulating, Polyethylene Glycols chemistry, Rhodamines chemistry, Transplantation, Heterologous, Nanoparticles chemistry, Silicon Dioxide chemistry
- Abstract
Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications.
- Published
- 2013
- Full Text
- View/download PDF
49. Understanding the photophysical properties of coumarin-based Pluronic-silica (PluS) nanoparticles by means of time-resolved emission spectroscopy and accurate TDDFT/stochastic calculations.
- Author
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Pedone A, Gambuzzi E, Barone V, Bonacchi S, Genovese D, Rampazzo E, Prodi L, and Montalti M
- Subjects
- Fluorescent Dyes chemical synthesis, Fluorescent Dyes chemistry, Quantum Theory, Coumarins chemistry, Nanoparticles chemistry, Poloxamer chemistry, Silicon Dioxide chemistry
- Abstract
The photophysical properties of two 7-aminocoumarin molecules with flexible and rigid alkyl moieties at the 7-nitrogen atom have been investigated in ethanol and in Pluronic-silica nanoparticles (PluS NPs) by means of time-resolved emission spectroscopy (TRES) and time-dependent density functional theory (TDDFT). Although the two coumarin derivatives have very different photophysical properties in solution, they show quite similar photophysical behaviour when embedded into the NPs, where an increase in the fluorescence quantum yield of about 10 times was observed for the more flexible molecule. TDDFT calculations employing long-range corrected functionals and with proper account of environmental effects reveal that the formation of an accessible twisted-intramolecular charge transfer state (TICT) is possible for 7-aminocoumarin molecules with flexible alkyl groups in fluid solution, where a conical intersection between the S1 and S0 states is observed at a dihedral angle of about 80°. The excited state dynamics of the population density of this reaction coordinate in ethanol and in silica NPs investigated through the resolution of a generalized Smoulochowsky equation shows that this deactivation mechanism is drastically hampered in a silica matrix, in good agreement with experimental evidence. Steady state and time resolved measurements also suggest that at high concentration for both the dyes intermolecular interactions into the silica matrix lead to fluorescence quenching. TDDFT/PCM calculations clearly indicate that the strong quenching and red shift observed is imputable to the formation of excimers with CT character after absorption of the monomeric species.
- Published
- 2013
- Full Text
- View/download PDF
50. Drug-loaded fluorescent cubosomes: versatile nanoparticles for potential theranostic applications.
- Author
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Murgia S, Bonacchi S, Falchi AM, Lampis S, Lippolis V, Meli V, Monduzzi M, Prodi L, Schmidt J, Talmon Y, and Caltagirone C
- Subjects
- Animals, Antineoplastic Agents, Phytogenic pharmacology, Cell Survival drug effects, Drug Compounding methods, Fluorescein, Fluorescent Dyes, Glycerides pharmacology, Humans, Mice, Microscopy, Fluorescence, NIH 3T3 Cells, Nanoparticles ultrastructure, Particle Size, Phosphatidylcholines, Precision Medicine, Quercetin pharmacology, Single-Cell Analysis, Glycerides chemistry, Nanoparticles chemistry
- Abstract
In this work, monoolein-based cubosomes were doped with two fluorescent probes, namely, fluorescein and dansyl, properly modified with a hydrocarbon chain to increase their encapsulation efficiency within the monoolein palisade. The same nanocarriers were also loaded with quercetin, a hydrophobic molecule with potential anticancer activity. Particularly, the cubosomes doped with the modified fluorescein probe were successfully exploited for single living cell imaging. The physicochemical and photophysical characterizations reported here, along with the well-known ability of cubosomes in hosting molecules with pharmaceutical interest, strongly encourage the use of these innovative fluorescent nanocarriers for theranostic purposes.
- Published
- 2013
- Full Text
- View/download PDF
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