Dopamine (DA) is one of the main neurotransmitters found in the central nervous system and has a vital role in the function of dopaminergic (DArgic) neurons. A progressive loss of this specific subset of cells is one of the hallmarks of age-related neurodegenerative disorders such as Parkinson’s disease (PD). Symptomatic therapy for PD has been centered in the precursor l -DOPA administration, an amino acid precursor of DA that crosses the blood–brain barrier (BBB) while DA does not, although this approach presents medium- to long-term side effects. To overcome this limitation, DA-nanoencapsulation therapies are actively being searched as an alternative for DA replacement. However, overcoming the low yield of encapsulation and/or poor biodistribution/bioavailability of DA is still a current challenge. Herein, we report the synthesis of a family of neuromelanin bioinspired polymeric nanoparticles. Our system is based on the encapsulation of DA within nanoparticles through its reversible coordination complexation to iron metal nodes polymerized with a bis-imidazol ligand. Our methodology, in addition to being simple and inexpensive, results in DA loading efficiencies of up to 60%. In vitro , DA nanoscale coordination polymers (DA-NCPs) exhibited lower toxicity, degradation kinetics, and enhanced uptake by BE(2)-M17 DArgic cells compared to free DA. Direct infusion of the particles in the ventricle of rats in vivo showed a rapid distribution within the brain of healthy rats, leading to an increase in striatal DA levels. More importantly, after 4 days of nasal administrations with DA-NCPs equivalent to 200 μg of the free drug per day, the number and duration of apomorphine-induced rotations was significantly lower from that in either vehicle or DA-treated rats performed for comparison purposes. Overall, this study demonstrates the advantages of using nanostructured DA for DA-replacement therapy.

In the last years, extensive attention has been paid on designing and developing functional imaging contrast agents for providing accurate non-invasive evaluation of pathology in vivo. However, the issue of false-positives or ambiguous imaging and the lack of a robust strategy for simultaneous dual-mode imaging remain to be fully addressed. One effective strategy for improving it is to rationally design magnetic resonance imaging (MRI) contrast agents (CAs) with intrinsic T 1 /T 2 dual-mode imaging features. In this work, the development and characterization of one-pot synthesized nanostructured coordination polymers (NCPs) which exhibit dual mode T 1 /T 2 MRI contrast behaviour is described. The resulting material comprises the combination of different paramagnetic ions (Fe 3+ , Gd 3+ , Mn 2+) with selected organic ligands able to induce the polymerization process and nanostructure stabilization. Among them, the Febased NCPs showed the best features in terms of colloidal stability, low toxicity, and dual T 1 /T 2 MRI contrast performance overcoming the main drawbacks of reported CAs. The dual-mode CA capability was evaluated by different means: in vitro phantoms, ex vivo and in vivo MRI, using a preclinical model of murine glioblastoma. Surprisingly, the in vivo MRI shows its T 1 and T 2 high contrast potential, allowing simultaneous recording of positive and negative contrast images in a very short period of time while being safer for the body. Moreover, the biodistribution assays reveals the persistence of the nanoparticles in the tumor and subsequent gradual clearance denoting their biodegradability. After a comparative study with commercial CAs, the results suggest these nanoplatforms as promising candidates for the development of dual-mode MRI CAs with clear advantages.

Abstract:The covalent functionalization of surfaces with molecules capable of providing new properties to the treated substrate, such as hydrophobicity or bioactivity, has been attracting a lot of interest in the last decades. For achieving this goal, the generation of a universally functionalizable primer coating in one-pot reaction and under relatively mild conditions is especially attractive due to its potential versatility and ease of application. The aim of the present work is to obtain such a functionalizable coating by a cross-linking reaction between pyrocatechol and hexamethylenediamine (HDMA) under oxidizing conditions. For demonstrating the efficacy of this approach, different substrates (glass, gold, silicon, and fabric) have been coated and later functionalized with two different alkylated species (1-hexadecanamine and stearoyl chloride). The success of their attachment has been demonstrated by evaluating the hydrophobicity conferred to the surface by contact angle measurements. Interestingly, these results, together with its chemical characterization by means of X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR), have proven that the reactivity of the primer coating towards the functionalizing agent can be tuned in function of its generation time.

A novel dual T1/T21H-MRI contrast agent based on the encapsulation of super-paramagnetic iron oxide nanoparticles (SPIONs) with an iron coordination polymer is proposed.

Development of novel 2D materials with singular and thrilling properties has aroused large interest due to the novel unexpected applications that can be derived from there. In this sense, coordination polymers (CPs) have appeared as matching candidates thanks to their rational chemical design and the added-value properties given by the presence of metal ions. This is the case of switchable spin crossover systems that have been proposed as excellent candidates for data storage or sensing, among others. Here we report the delamination of crystals of the 2D spin crossover (SCO) {[Fe(L1)2](ClO4)2}∝ (1) CP by liquid-phase exfoliation (LPE) in water. The application of this top-down technique results in the formation of flakes with controlled thicknesses, down to 1-2 nm thick (mostly mono-and bi-layer), that retain the chemical composition and SCO interconversion of the bulk material. Moreover, these flakes can be handled as stable colloidal dispersions for many days. This allows for a controlled transfer to solid substrates and the formation of thermochromic polymeric films as a proof-of-concept of device. These first results will definitely open new venues and opportunities for the investigation and future integration of these original switchable 2D materials in devices.

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The validation of metal–phenolic nanoparticles (MPNs) in preclinical imaging studies represents a growing field of interest due to their versatility in forming predesigned structures with unique properties. Before MPNs can be used in medicine, their pharmacokinetics must be optimized so that accumulation in nontargeted organs is prevented and toxicity is minimized. Here, we report the fabrication of MPNs made of a coordination polymer core that combines In­(III), Cu­(II), and a mixture of the imidazole 1,4-bis­(imidazole-1-ylmethyl)-benzene and the catechol 3,4-dihydroxycinnamic acid ligands. Furthermore, a phenolic-based coating was used as an anchoring platform to attach poly­(ethylene glycol) (PEG). The resulting MPNs, with effective hydrodynamic diameters of around 120 nm, could be further derivatized with surface-embedded molecules, such as folic acid, to facilitate in vivo targeting and multifunctionality. The prepared MPNs were evaluated for in vitro plasma stability, cytotoxicity, and cell internalization and found to be biocompatible under physiological conditions. First, biomedical evaluations were then performed by intrinsically incorporating trace amounts of the radioactive metals 111In or 64Cu during the MPN synthesis directly into their polymeric matrix. The resulting particles, which had identical physicochemical properties to their nonradioactive counterparts, were used to perform in vivo single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in tumor-bearing mice. The ability to incorporate multiple metals and radiometals into MPNs illustrates the diverse range of functional nanoparticles that can be prepared with this approach and broadens the scope of these nanoconstructs as multimodal preclinical imaging agents.

Two novel cadmium-based 2D coordination polymers have been synthesized and characterized. Experimental results evidence that the best delamination processes occurs when weak interactions dominate the cohesion between layers, modulated by solvent molecules occluded within the crystalline network. In this case, the delamination of the crystals occurs spontaneously in water whereas nanoflakes though they can also be obtained by ultrasound-assisted liquid phase exfoliation in solvents such as ethanol or acetone. However, when interlayer solvent molecules are coordinated to metal centers, more robust structures are obtained, making very difficult the delamination process. This study shows how the physicochemical properties and structure of the bulk crystals determine the success of the exfoliation process in which the sonication method and type of solvent used are critical parameters. These systems offer also platform to study different experimental parameters and approaches (ultrasound bath vs. probe tip) on the delamination of these 2D materials.