Reduction of the two-photon temporal distinguishability for measurement-device-independent quantum key distribution.

Measurement-device-independent quantum key distribution (MDI-QKD) has been proven to protect legitimate users from attacks against measurement devices. The MDI-QKD requires that the two photons arriving at the instrument be indistinguishable. Precise time control is required to eliminate the distinguishability due to differences in photon arrival times. In the conventional methods, the time difference between photons is measured at a measuring instrument (Charlie), and a control signal is transmitted to the users (Alice and Bob). However, this method requires a long feedback loop, and the control may become unstable for long-distance transmission. This article proposes a method in which the photon arrival time difference is detected and controlled at Charlie. The reference signal for the time control is generated by an optical frequency comb in synchronization with the quantum signal. Therefore, the quantum signal photons can also be synchronized by synchronizing the reference signal pulses. A proof-of-principle experiment confirmed that the time synchronization accuracy required for protocol execution could be obtained. This proposal simplifies the implementation of the MDI-QKD.

Fluorescent naphthalimide boronates as theranostics: structural investigations, confocal fluorescence and multiphoton fluorescence lifetime imaging microscopy in living cells.

New design and synthetic strategies were developed to generate functional phenyl boronic acid (BA)-based fluorescent probes incorporating the 1,8-naphthalimide (NI) tag. This fluorescent core was anchored onto the BA unit through small organic linkers consisting of nitrogen groups which can arrest, and internally stabilise the phenyl-boronate units. The newly synthesised fluorophores were characterised spectroscopically by NMR spectroscopy and mass spectrometry and evaluated for their ability to bind to a naturally occurring polysaccharide, ß-d-glucan in DMSO and simultaneously as act as in vitro cell imaging reagents. The uptake of these new NI-boronic acid derivatives was studied living cancer cells (HeLa, PC-3) in the presence, and absence, of ß-d-glucan. Time-correlated single-photon counting (TCSPC) of DMSO solutions and two-photon fluorescence-lifetime imaging microscopy (FLIM) techniques allowed an insight into the probes' interaction with their environment. Their cellular uptake and distributions were imaged using laser scanning confocal fluorescence microscopy under single- and two-photon excitation regimes (λmax 910 nm). FLIM facilitated the estimation of the impact of the probe's cellular surroundings using the fluorophore lifetime. The extent to which this was mediated by the ß-d-glucan was visualised by 2-photon FLIM in living cells. The fluorescence lifetime observed under a range of temperatures varied appreciably, indicating that changes in the environment can be sensed by these probes. In all cases, the cellular membrane penetration of these new probes was remarkable even under variable temperature conditions and localisation was widely concentrated in the cellular cytoplasm, without specific organelle trapping: we conclude that these new probes show promise for cellular imaging in living cancer cells.

Structural and Functional Diversity in Rigid Thiosemicarbazones with Extended Aromatic Frameworks: Microwave-Assisted Synthesis and Structural Investigations.

The long-standing interest in thiosemicarbazones (TSCs) has been largely driven by their potential toward theranostic applications including cellular imaging assays and multimodality imaging. We focus herein on the results of our new investigations into: (a) the structural chemistry of a family of rigid mono(thiosemicarbazone) ligands characterized by extended and aromatic backbones and (b) the formation of their corresponding thiosemicarbazonato Zn(II) and Cu(II) metal complexes. The synthesis of new ligands and their Zn(II) complexes was performed using a rapid, efficient and straightforward microwave-assisted method which superseded their preparation by conventional heating. We describe hereby new microwave irradiation protocols that are suitable for both imine bond formation reactions in the thiosemicabazone ligand synthesis and for Zn(II) metalation reactions. The new thiosemicarbazone ligands, denoted HL, mono(4-R-3-thiosemicarbazone)quinone, and their corresponding Zn(II) complexes, denoted ZnL2, mono(4-R-3-thiosemicarbazone)quinone, where R = H, Me, Ethyl, Allyl, and Phenyl, quinone = acenapthnenequinone (AN), aceanthrenequinone (AA), phenanthrenequinone (PH), and pyrene-4,5-dione (PY) were isolated and fully characterized spectroscopically and by mass spectrometry. A plethora of single crystal X-ray diffraction structures were obtained and analyzed and the geometries were also validated by DFT calculations. The Zn(II) complexes presented either distorted octahedral geometry or tetrahedral arrangements of the O/N/S donors around the metal center. The modification of the thiosemicarbazide moiety at the exocyclic N atoms with a range of organic linkers was also explored, opening the way to bioconjugation protocols for these compounds. The radiolabeling of these thiosemicarbazones with 64Cu was achieved under mild conditions for the first time: this cyclotron-available radioisotope of copper (t1/2 = 12.7 h; ß+ 17.8%; ß- 38.4%) is well-known for its proficiency in positron emission tomography (PET) imaging and for its theranostic potential, on the basis of the preclinical and clinical cancer research of established bis(thiosemicarbazones), such as the hypoxia tracer 64Cu-labeled copper(diacetyl-bis(N4-methylthiosemicarbazone)], [64Cu]Cu(ATSM). Our labeling reactions proceeded in high radiochemical incorporation (>80% for the most sterically unencumbered ligands) showing promise of these species as building blocks for theranostics and synthetic scaffolds for multimodality imaging probes. The corresponding "cold" Cu(II) metalations were also performed under the mild conditions mimicking the radiolabeling protocols. Interestingly, room temperature or mild heating led to Cu(II) incorporation in the 1:1, as well as 1:2 metal: ligand ratios in the new complexes, as evident from extensive mass spectrometry investigations backed by EPR measurements, and the formation of Cu(L)2-type species prevails, especially for the AN-Ph thiosemicarbazone ligand (L-). The cytotoxicity levels of a selection of ligands and Zn(II) complexes in this class were further tested in commonly used human cancer cell lines (HeLa, human cervical cancer cells, and PC-3, human prostate cancer cells). Tests showed that their IC50 levels are comparable to that of the clinical drug cis-platin, evaluated under similar conditions. The cellular internalizations of the selected ZnL2-type compounds Zn(AN-Allyl)2, Zn(AA-Allyl)2, Zn(PH-Allyl)2, and Zn(PY-Allyl)2 were evaluated in living PC-3 cells using laser confocal fluorescent spectroscopy and these experiments showed exclusively cytoplasmic distributions.

Unraveling the Chemistry of meso-Cl Tricarbocyanine Dyes in Conjugation Reactions for the Creation of Peptide Bonds.

Tricarbocyanine dyes have become popular tools in life sciences and medicine. Their near-infrared (NIR) fluorescence makes them ideal agents for imaging of thick specimens or in vivo imaging, e.g., in fluorescence-guided surgery. Among other types of cyanine dyes, meso-Cl tricarbocyanine dyes have received a surge of interest, as it emerged that their high reactivity makes them inherently tumor-targeting. As such, significant research efforts have focused on conjugating these to functional moieties. However, the syntheses generally suffer from low yields. Hereby, we report on the reaction of meso-Cl dyes with a small selection of coupling reagents to give the corresponding keto-polymethines, potentially explaining low yields and the prevalence of monofunctionalized cyanine conjugates in the current state of the art of functional near-infrared dyes. We present the synthesis and isolation of the first keto-polymethine-based conjugate and present preliminary investigation in the prostate cancer cell lines PC3 and DU145 by confocal microscopy and discuss changes to optical properties in biological media.

Corrigendum: Nano-Theranostics for the Sensing, Imaging and Therapy of Prostate Cancers.

[This corrects the article DOI: 10.3389/fchem.2022.830133.].

Nano-Theranostics for the Sensing, Imaging and Therapy of Prostate Cancers.

We highlight hereby recent developments in the emerging field of theranostics, which encompasses the combination of therapeutics and diagnostics in a single entity aimed for an early-stage diagnosis, image-guided therapy as well as evaluation of therapeutic outcomes of relevance to prostate cancer (PCa). Prostate cancer is one of the most common malignancies in men and a frequent cause of male cancer death. As such, this overview is concerned with recent developments in imaging and sensing of relevance to prostate cancer diagnosis and therapeutic monitoring. A major advantage for the effective treatment of PCa is an early diagnosis that would provide information for an appropriate treatment. Several imaging techniques are being developed to diagnose and monitor different stages of cancer in general, and patient stratification is particularly relevant for PCa. Hybrid imaging techniques applicable for diagnosis combine complementary structural and morphological information to enhance resolution and sensitivity of imaging. The focus of this review is to sum up some of the most recent advances in the nanotechnological approaches to the sensing and treatment of prostate cancer (PCa). Targeted imaging using nanoparticles, radiotracers and biomarkers could result to a more specialised and personalised diagnosis and treatment of PCa. A myriad of reports has been published literature proposing methods to detect and treat PCa using nanoparticles but the number of techniques approved for clinical use is relatively small. Another facet of this report is on reviewing aspects of the role of functional nanoparticles in multimodality imaging therapy considering recent developments in simultaneous PET-MRI (Positron Emission Tomography-Magnetic Resonance Imaging) coupled with optical imaging in vitro and in vivo, whilst highlighting feasible case studies that hold promise for the next generation of dual modality medical imaging of PCa. It is envisaged that progress in the field of imaging and sensing domains, taken together, could benefit from the biomedical implementation of new synthetic platforms such as metal complexes and functional materials supported on organic molecular species, which can be conjugated to targeting biomolecules and encompass adaptable and versatile molecular architectures. Furthermore, we include hereby an overview of aspects of biosensing methods aimed to tackle PCa: prostate biomarkers such as Prostate Specific Antigen (PSA) have been incorporated into synthetic platforms and explored in the context of sensing and imaging applications in preclinical investigations for the early detection of PCa. Finally, some of the societal concerns around nanotechnology being used for the detection of PCa are considered and addressed together with the concerns about the toxicity of nanoparticles-these were aspects of recent lively debates that currently hamper the clinical advancements of nano-theranostics. The publications survey conducted for this review includes, to the best of our knowledge, some of the most recent relevant literature examples from the state-of-the-art. Highlighting these advances would be of interest to the biomedical research community aiming to advance the application of theranostics particularly in PCa diagnosis and treatment, but also to those interested in the development of new probes and methodologies for the simultaneous imaging and therapy monitoring employed for PCa targeting.

Functional, Aromatic, and Fluorinated Monothiosemicarbazones: Investigations into Their Structures and Activity toward the Gallium-68 Incorporation by Microwave Irradiation.

We report on the synthesis and spectroscopic characterization of a new series of coordinating monothiosemicarbazones incorporating aromatic backbones, featuring O/N/S donor centers monosubstituted with different aliphatic, aromatic, fluorinated, and amine-functionalized groups at their N centers. Their ability to bind metal ions such as Zn(II) and Ga(III) was explored, and the formation of two different coordination isomers of the Zn(II) complex was demonstrated by X-ray diffraction studies using synchrotron radiation. These studies showed the planar geometry for the coordinated mono(thiosemicarbazone) ligand and that the metal center can adopt either a heavily distorted tetrahedral Zn center (placed in an N/S/S/N environment, with CN = 4) or a pseudo-octahedral geometry, where the Zn(II) center is in the O/N/S/S/N/O environment, and CN = 6. Furthermore, 2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide (MTT) assays and cellular imaging in living cells were subsequently performed in two different cancer cell lines: PC-3 (a standard cell line derived from a bone metastasis of a stage IV prostate cancer) and EMT6 (a commercial murine mammary carcinoma cell line). The radiolabeling of new functional and aromatic monothiosemicarbazones with either gallium-68 (under pH control) or fluorine-18 is discussed. The potential of this class of compounds to act as synthetic scaffolds for molecular imaging agents of relevance to positron emission tomography was evaluated in vitro, and the cellular uptake of a simultaneously fluorinated and [68Ga]-labeled mono(thiosemicarbazone) was investigated and is reported here.

Hybrid Hierarchical Heterostructures of Nanoceramic Phosphors as Imaging Agents for Multiplexing and Living Cancer Cells Translocation.

Existing fluorescent labels used in life sciences are based on organic compounds with limited lifetime or on quantum dots which are either expensive or toxic and have low kinetic stability in biological environments. To address these challenges, luminescent nanomaterials have been conceived as hierarchical, core-shell structures with spherical morphology and highly controlled dimensions. These tailor-made nanophosphors incorporate Ln:YVO4 nanoparticles (Ln = Eu(III) and Er(III)) as 50 nm cores and display intense and narrow emission maxima centered at ∼565 nm. These cores can be encapsulated in silica shells with highly controlled dimensions as well as functionalized with chitosan or PEG5000 to reduce nonspecific interactions with biomolecules in living cells. Confocal fluorescence microscopy in living prostate cancer cells confirmed the potential of these platforms to overcome the disadvantages of commercial fluorophores and their feasibility as labels for multiplexing, biosensing, and imaging in life science assays.

Structural Investigations, Cellular Imaging, and Radiolabeling of Neutral, Polycationic, and Polyanionic Functional Metalloporphyrin Conjugates.

Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin-metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having "true" theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary in vitro and in vivo uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing in vitro confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using in silico approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and 111In[In] or 68Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for in vivo studies, likely because the presence of the peptide changed the behavior of the TPP-NH2 synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.

Directed Molecular Stacking for Engineered Fluorescent Three-Dimensional Reduced Graphene Oxide and Coronene Frameworks.

Three-dimensional fluorescent graphene frameworks with controlled porous morphologies are of significant importance for practical applications reliant on controlled structural and electronic properties, such as organic electronics and photochemistry. Here we report a synthetically accessible approach concerning directed aromatic stacking interactions to give rise to new fluorogenic 3D frameworks with tuneable porosities achieved through molecular variations. The binding interactions between the graphene-like domains present in the in situ-formed reduced graphene oxide (rGO) with functional porphyrin molecules lead to new hybrids via an unprecedented solvothermal reaction. Functional free-base porphyrins featuring perfluorinated aryl groups or hexyl chains at their meso- and ß-positions were employed in turn to act as directing entities for the assembly of new graphene-based and foam-like frameworks and of their corresponding coronene-based hybrids. Investigations in the dispersed phase and in thin-film by XPS, SEM and FLIM shed light onto the nature of the aromatic stacking within functional rGO frameworks (denoted rGOFs) which was then modelled semi-empirically and by DFT calculations. The pore sizes of the new emerging reduced graphene oxide hybrids are tuneable at the molecular level and mediated by the bonding forces with the functional porphyrins acting as the "molecular glue". Single crystal X-ray crystallography described the stacking of a perfluorinated porphyrin with coronene, which can be employed as a molecular model for understanding the local aromatic stacking order and charge transfer interactions within these rGOFs for the first time. This opens up a new route to controllable 3D framework morphologies and pore size from the Ångstrom to the micrometre scale. Theoretical modelling showed that the porosity of these materials is mainly due to the controlled inter-planar distance between the rGO, coronene or graphene sheets. The host-guest chemistry involves the porphyrins acting as guests held through π-π stacking, as demonstrated by XPS. The objective of this study is also to shed light into the fundamental localised electronic and energy transfer properties in these new molecularly engineered porous and fluorogenic architectures, aiming in turn to understand how functional porphyrins may exert stacking control over the notoriously disordered local structure present in porous reduced graphene oxide fragments. By tuning the porosity and the distance between the graphene sheets using aromatic stacking with porphyrins, it is also possible to tune the electronic structure of the final nanohybrid material, as indicated by FLIM experiments on thin films. Such nanohybrids with highly controlled pores dimensions and morphologies open the way to new design and assembly of storage devices and applications incorporating π-conjugated molecules and materials and their π-stacks may be relevant towards selective separation membranes, water purification and biosensing applications.

Multiphoton fluorescence lifetime imaging microscopy (FLIM) and super-resolution fluorescence imaging with a supramolecular biopolymer for the controlled tagging of polysaccharides.

A new supramolecular polysaccharide complex, comprising a functionalised coumarin tag featuring a boronic acid and ß-d-glucan (a natural product extract from barley, Hordeum Vulgare) was assembled based on the ability of the boronate motif to specifically recognise and bind to 1,2- or 1,3-diols in water. The complexation ratio of the fluorophore : biopolymer strand was determined from fluorescence titration experiments in aqueous environments and binding isotherms best described this interaction using a 2 : 1 model with estimated association constants of K2:1a1 = 5.0 × 104 M-1 and K2:1a2 = 3.3 × 1011 M-1. The resulting hybrid (denoted 5@ß-d-glucan) was evaluated for its cellular uptake as an intact functional biopolymer and its distribution compared to that of the pinacol-protected coumarin boronic acid derivative using two-photon fluorescence lifetime imaging microscopy (FLIM) in living cells. The new fluorescent ß-d-glucan conjugate has a high kinetic stability in aqueous environments with respect to the formation of the free boronic acid derivative compound 5 and retains fluorescence emissive properties both in solution and in living cells, as shown by two-photon fluorescence spectroscopy coupled with time-correlated single photon counting (TCSPC). Super-resolution fluorescence imaging using Airyscan detection as well as TM AFM and Raman spectroscopy investigations confirmed the formation of fluorescent and nano-dimensional aggregates of up to 20 nm dimensions which self-assemble on several different inert surfaces, such as borosilicate glass and mica surfaces, and these aggregates can also be observed within living cells with optical imaging techniques. The cytoplasmic distribution of the 5@ß-d-glucan complex was demonstrated in several different cancer cell lines (HeLa and PC-3) as well as in healthy cells (J774.2 macrophages and FEK-4). Both new compounds (pinacol protected boronated coumarin) 5-P and its complex hybrid 5@ß-d-glucan successfully penetrate cellular membranes with the minimum morphological alterations to cells and distribute evenly in the cytoplasm. The glucan biopolymer retains its activity towards macrophages in the presence of the coumarin tag functionality, demonstrating the potential of this natural ß-d-glucan to act as a functional self-assembled theranostic scaffold capable of mediating the delivery of anchored small organic molecules with imaging and drug delivery applications.

Extracellular Electrophysiology in the Prostate Cancer Cell Model PC-3.

Although prostate cancer is one of the most common cancers in the male population, its basic biological function at a cellular level remains to be fully understood. This lack of in depth understanding of its physiology significantly hinders the development of new, targeted and more effective treatment strategies. Whilst electrophysiological studies can provide in depth analysis, the possibility of recording electrical activity in large populations of non-neuronal cells remains a significant challenge, even harder to address in the picoAmpere-range, which is typical of cellular level electrical activities. In this paper, we present the measurement and characterization of electrical activity of populations of prostate cancer cells PC-3, demonstrating for the first time a meaningful electrical pattern. The low noise system used comprises a multi-electrode array (MEA) with circular gold electrodes on silicon oxide substrates. The extracellular capacitive currents present two standard patterns: an asynchronous sporadic pattern and a synchronous quasi-periodic biphasic spike pattern. An amplitude of ±150 pA, a width between 50⁻300 ms and an inter-spike interval around 0.5 Hz characterize the quasi-periodic spikes. Our experiments using treatment of cells with Gd³âº, known as an inhibitor for the Ca²âº exchanges, suggest that the quasi-periodic signals originate from Ca²âº channels. After adding the Gd³âº to a population of living PC-3 cells, their electrical activity considerably decreased; once the culture was washed, thus eliminating the Gd³âº containing medium and addition of fresh cellular growth medium, the PC-3 cells recovered their normal electrical activity. Cellular viability plots have been carried out, demonstrating that the PC-3 cells remain viable after the use of Gd³âº, on the timescale of this experiment. Hence, this experimental work suggests that Ca²âº is significantly affecting the electrophysiological communication pattern among PC-3 cell populations. Our measuring platform opens up new avenues for real time and highly sensitive investigations of prostate cancer signalling pathways.

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics.

Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab-scale, batch-to-batch reproducible copper-64- and gallium-68-radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water-dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes 64Cu (t1/2=12.7 h) and 68Ga (t1/2=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC-3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO2 matrix represents an ideal platform for the incorporation of 64Cu and 68Ga radioisotopes with high radiolabelling incorporation.

Encapsulation of Cadmium Selenide Nanocrystals in Biocompatible Nanotubes: DFT Calculations, X-ray Diffraction Investigations, and Confocal Fluorescence Imaging.

The encapsulation of CdSe nanocrystals within single-walled carbon nanotube (SWNT) cavities of varying dimensions at elevated temperatures under strictly air-tight conditions is described for the first time. The structures of CdSe nanocrystals under confinement inside SWNTs was established in a comprehensive study, combining both experimental and DFT theoretical investigations. The calculated binding energies show that all considered polymorphs [(3:3), (4:4), and (4:2)] may be obtained experimentally. The most thermodynamically stable structure (3:3) is directly compared to the experimentally observed CdSe structures inside carbon nanotubes. The gas-phase DFT-calculated energy difference between "free" 3:3 and 4:2 structures (whereby 3:3 models a novel tubular structure in which both Cd and Se form three coordination, as observed experimentally for HgTe inside SWNT, and 4:2 is a motif derived from the hexagonal CuI bulk structure in which both Cd and Se form 4 or 2 coordination) is surprisingly small, only 0.06 eV per formula unit. X-ray powder diffraction, Raman spectroscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray analyses led to the full characterization of the SWNTs filled with the CdSe nanocrystals, shedding light on the composition, structure, and electronic interactions of the new nanohybrid materials on an atomic level. A new emerging hybrid nanomaterial, simultaneously filled and beta-d-glucan coated, was obtained by using pristine nanotubes and bulk CdSe powder as starting materials. This displayed fluorescence in water dispersions and unexpected biocompatibility was found to be mediated by beta-d-glucan (a biopolymer extracted from barley) with respect to that of the individual inorganic material components. For the first time, such supramolecular nanostructures are investigated by life-science techniques applied to functional nanomaterial characterization, opening the door for future nano-biotechnological applications.

Lysosomal tracking with a cationic naphthalimide using multiphoton fluorescence lifetime imaging microscopy.

A naphthalimide-based chemosensing motif turns ON the fluorescence emission in solution in the presence of aqueous iron(iii) chloride, and maintains this property in living cancer cells. The emission response to Fe(iii) ions occurs simultaneously with a change in pH. The protonation of methyl piperazine-conjugated naphthalimide promotes its lysosomal localisation as assessed by co-localisation tests and fluorescence lifetime imaging microscopy (FLIM) in vitro.

Fluorescence-Lifetime Imaging and Super-Resolution Microscopies Shed Light on the Directed- and Self-Assembly of Functional Porphyrins onto Carbon Nanotubes and Flat Surfaces.

Functional porphyrins have attracted intense attention due to their remarkably high extinction coefficients in the visible region and potential for optical and energy-related applications. Two new routes to functionalised SWNTs have been established using a bulky ZnII -porphyrin featuring thiolate groups at the periphery. We probed the optical properties of this zinc(II)-substituted, bulky aryl porphyrin and those of the corresponding new nano-composites with single walled carbon nanotube (SWNTs) and coronene, as a model for graphene. We report hereby on: i) the supramolecular interactions between the pristine SWNTs and ZnII -porphyrin by virtue of π-π stacking, and ii) a novel covalent binding strategy based on the Bingel reaction. The functional porphyrins used acted as dispersing agent for the SWNTs and the resulting nanohybrids showed improved dispersibility in common organic solvents. The synthesized hybrid materials were probed by various characterisation techniques, leading to the prediction that supramolecular polymerisation and host-guest functionalities control the fluorescence emission intensity and fluorescence lifetime properties. For the first time, XPS studies highlighted the differences in covalent versus non-covalent attachments of functional metalloporphyrins to SWNTs. Gas-phase DFT calculations indicated that the ZnII -porphyrin interacts non-covalently with SWNTs to form a donor-acceptor complex. The covalent attachment of the porphyrin chromophore to the surface of SWNTs affects the absorption and emission properties of the hybrid system to a greater extent than in the case of the supramolecular functionalisation of the SWNTs. This represents a synthetic challenge as well as an opportunity in the design of functional nanohybrids for future sensing and optoelectronic applications.

A fluorescent Arg-Gly-Asp (RGD) peptide-naphthalenediimide (NDI) conjugate for imaging integrin α(v)ß(3) in vitro.

We have developed a fluorescent peptide conjugate (TrpNDIRGDfK) based on the coupling of cyclo(RGDfK) to a new tryptophan-tagged amino acid naphthalenediimide (TrpNDI). Confocal fluorescence microscopy coupled with fluorescence lifetime imaging (FLIM) mapping, single and two-photon fluorescence excitation, lifetime components and corresponding decay profiles were used as parameters able to investigate qualitatively the cellular behavior regarding the molecular environment and biolocalisation of TrpNDI and TrpNDI-RGDfK in cancer cells.

Synthesis and evaluation of a boronate-tagged 1,8-naphthalimide probe for fluoride recognition.

A biocompatible fluoride receptor has been developed where the interaction between the boronic acid ester and amine (NH) results in fluoride ion selectivity and enhanced fluorescence quenching.

Metallic nanoparticles as synthetic building blocks for cancer diagnostics: from materials design to molecular imaging applications.

Metallic nanoparticles have been a matter of intense exploration within the last decade due to their potential to change the face of the medical world through their role as 'nanotheranostics'. Their envisaged capacity to act as synthetic platforms for a multimodal imaging approach to diagnosis and treatment of degenerative diseases, including cancer, remains a matter of lively debate. Certain synthetic metal-based nanomaterials, e.g. gold and iron oxide nanoparticles, are already in clinical use or under advanced preclinical investigations following in vitro and in vivo preclinical imaging success. We surveyed the recent publications landscape including those reported metallic nanoparticles having established applications in vivo, as well as some of the new metallic nanoparticles which, despite their potential as cancer nanodiagnostics, are currently awaiting in vivo evaluation. The objective of this review is to highlight the current metallic nanoparticles and/or alloys as well as their derivatives with multimodal imaging potential, focusing on their chemistry as a springboard to discussing their role in the future of nanomedicines design. We also highlight here some of the fundamentals of molecular and nano-imaging techniques of relevance to the metal-based colloids, alloys and metallic nanoparticles discerning their future prospects as cancer nanodiagnostics. The current approaches for metallic and alloy surface derivatisation, aiming to achieve functional and biocompatible materials for multimodal bioimaging applications, are discussed in order to bring about some new perspectives on the efficiency of metallic nanoparticles as synthetic scaffolds for imaging probe design and forecast their future use in medical imaging techniques (optical, CT, PET, SPECT and MRI).