Tripodal BODIPY-Tagged and Functional Molecular Probes: Synthesis, Computational Investigations and Explorations by Multiphoton Fluorescence Lifetime Imaging Microscopy.

A range of novel BODIPY derivatives with a tripodal aromatic core was synthesized and characterized spectroscopically. These new fluorophores showed promising features as probes for in vitro assays in live cells and offer strategic routes for further functionalization towards hybrid nanomaterials. Incorporation of biotin tags facilitated proof-of-concept access to targeted bioconjugates as molecular probes. Computational explorations using DFT and TD-DFT calculations identified the most stable tripodal linker conformations and predicted their absorption and emission behavior. The uptake and speciation of these molecules in living prostate cancer cells was imaged by single- and two-photon excitation techniques coupled with two-photon fluorescence lifetime imaging (2P FLIM).

Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography.

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification due to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture, and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here, we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural l-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale.

Functional Diversity in Radiolabeled Nanoceramics and Related Biomaterials for the Multimodal Imaging of Tumors.

Nanotechnology advances have the potential to assist toward the earlier detection of diseases, giving increased accuracy for diagnosis and helping to personalize treatments, especially in the case of noncommunicative diseases (NCDs) such as cancer. The main advantage of nanoparticles, the scaffolds underpinning nanomedicine, is their potential to present multifunctionality: synthetic nanoplatforms for nanomedicines can be tailored to support a range of biomedical imaging modalities of relevance for clinical practice, such as, for example, optical imaging, computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). A single nanoparticle has the potential to incorporate myriads of contrast agent units or imaging tracers, encapsulate, and/or be conjugated to different combinations of imaging tags, thus providing the means for multimodality diagnostic methods. These arrangements have been shown to provide significant improvements to the signal-to-noise ratios that may be obtained by molecular imaging techniques, for example, in PET diagnostic imaging with nanomaterials versus the cases when molecular species are involved as radiotracers. We surveyed some of the main discoveries in the simultaneous incorporation of nanoparticulate materials and imaging agents within highly kinetically stable radio-nanomaterials as potential tracers with (pre)clinical potential. Diversity in function and new developments toward synthesis, radiolabeling, and microscopy investigations are explored, and preclinical applications in molecular imaging are highlighted. The emphasis is on the biocompatible materials at the forefront of the main preclinical developments, e.g., nanoceramics and liposome-based constructs, which have driven the evolution of diagnostic radio-nanomedicines over the past decade.

Surface-controlled spatially heterogeneous physical properties of a supramolecular gel with homogeneous chemical composition.

Controlling supramolecular self-assembly across multiple length scales to prepare gels with localised properties is challenging. Most strategies concentrate on fabricating gels with heterogeneous components, where localised properties are generated by the stimuli-responsive component. Here, as an alternative approach, we use a spiropyran-modified surface that can be patterned with light. We show that light-induced differences in surface chemistry can direct the bulk assembly of a low molecular weight gelator, 2-NapAV, meaning that mechanical gel properties can be controlled by the surface on which the gel is grown. Using grazing incidence X-ray diffraction and grazing incidence small angle X-ray scattering, we demonstrate that the origin of the different gel properties relates to differences in the architectures of the gels. This provides a new method to prepare a single domain (i.e., chemically homogeneous) hydrogel with locally controlled (i.e., mechanically heterogeneous) properties.

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.