Syringeable Self-Organizing Gels that Trigger Gold Nanoparticle Formation for Localized Thermal Ablation

Block copolymer dispersions that form gels at body temperature and that additionally are able to reduce a gold salt to nanoparticles (AuNPs) directly in the final formulation under mild conditions were designed as hybrid depots for photothermal therapy. The in situ gelling systems may retain AuNPs in the application zone for a long time so that localized elevations of temperature can be achieved each time the zone is irradiated. To carry out the work, dispersions were prepared covering a wide range of poloxamine Tetronic 1307:gold salt molar ratios in NaCl media (also varying from pure water to hypertonic solution). Even at copolymer concentrations well above the critical micelle concentration, the reducing power of the copolymer was maintained, and AuNPs were formed in few hours without extra additives. Varying the copolymer and NaCl concentrations allowed a fine tuning of nanoparticles’ shape from spherical to triangular nanoplates, which determined that the surface plasmon resonance showed a maximum intensity at 540 nm or at 1000 nm, respectively. The information gathered on the effects of (i) the poloxamine concentration on AuNPs’ size and shape under isotonic conditions, (ii) the AuNPs on the temperature-induced gelling transition, and (iii) the gel properties on the photothermal responsiveness of the AuNPs during successive irradiation cycles may help the rational design of one-pot gels with built-in temperature and light responsiveness.This research was funded by MINECO (SAF2017-83118-R; MAT2016-80266-R), Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia (Grupo de Referencia Competitiva ED431C 2016/008; Agrupación Estratégica en Materiales-AEMAT ED431E 2018/08), and FEDER (Spain). S.C.-M. acknowledges a Xunta de Galicia predoctoral grantS

The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG‐Dendritic GATG Copolymers

This is the peer-reviewed version of the following article: Fernandez-Villamarin, M., Sousa-Herves, A., Correa, J., Munoz, E., Taboada, P., Riguera, R., & Fernandez-Megia, E. (2016). The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG-Dendritic GATG Copolymers. Chemnanomat, 2(5), 437-446, which has been published in final form at https://doi.org/10.1002/cnma.201600008. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingA general synthetic strategy to polyethylene glycol (PEG)‐dendritic block copolymers of the GATG (gallic acid–triethylene glycol) family is described from commercially available PEG of different molecular weights and architectures. Glycosylation of the resulting azide‐terminated copolymers with fucose by copper‐catalyzed azide–alkyne cycloaddition (CuAAC) afforded a toolbox to study the effect of PEG on the multivalent binding with the lectin UEA‐I by surface plasmon resonance (SPR, on surface) and isothermal titration calorimetry (ITC, in solution). Our results indicate that PEG reduces the affinity of glycodendrimers towards lectins by steric hindrance in a molecular‐weight‐dependent fashion. Great differences were observed as a function of the PEG architecture, with diblock PEG‐dendritic copolymers benefiting from a positive entropic contribution (PEG folding), not seen in the dendritic‐PEG‐dendritic systems. The self‐inflicted steric stabilization of the PEGylated copolymers onto lectin clusters reveals the necessity of additional competitive experiments to fully assess the antiadhesive properties of PEG in biological environmentsSpanish Government. Grant Numbers: CTQ2015-69021-R, CTQ2012-34790, CTQ2014-61470-EXP Xunta de Galicia. Grant Number: GRC2014/040S

A heteronuclear ZnGd complex as a potential contrast agent for magnetic resonance imaging

The 20th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural ProductsA new ligand H3L, with internal compartments for allocating 3d metal ions and external donors to bind 4f ions, was synthesized and completely characterized. Reaction of H3L with zinc(II) and gadolin ium(III) salts allows isolating the heteronuclear complex {[ZnGd(HL)(NO3)(OAc)(CH3OH)](NO3)}∙6H2O (1·6H2O). The ability of 1·6H2O to act as a magnetic resonance imaging (MRI) contrast agent was evaluated and this study shows that both the transversal and longitudinal relaxivities are quite high but the T1/T2 ratio of 7.9 indicates that it could have even greater potential as a T2 contrast agen

On the structure and stability of novel cationic DPPC liposomes doped with gemini surfactants

A novel formulation of cationic liposomes was studied by mixing dipalmitoylphosphatidylcholine (DPPC) with tetradecyltrimethylammonium bromide gemini surfactants with different alkane spacer groups lengths attached to their ammonium head-groups. The physicochemical characterization of the cationic liposomes was obtained by combining experimental results from differential scanning microcalorimetry (DSC) with molecular dynamic simulations, in order to understand their structural configuration. An adapted Ising model was used to interpret the results in terms of cooperativity of the phase transitions. The gemini surfactants partition into the lipid bilayer of DPPC liposomes, and the induced changes in colloidal stability and phase transition were analyzed in detail. The DPPC liposomes became positively charged upon gemini surfactant partition, showing increased colloidal stability. Our results show significant differences in structural configuration between gemini surfactants with short and long spacer lengths. While gemini with shorter spacers allocate within the lipid bilayer with both headgroups in the same layer, geminis with longer spacers unexpectedly intercalate in the lipid membrane in a particular zig-zag configuration, with each headgroup located at a different side of the bilayer, altering the coupling degree parameters of the membrane’s phase transition. The extraordinary increase of colloidal stability of DPPC liposomes with gemini surfactants at very low molar ratio and the possibility to tune the physicochemical properties of the membrane by control de spacer length of the geminis opens new possibilities for cationic liposomal formulations with potential applications in vaccines, drug/gene delivery or biosensingThis work was supported by the Spanish Research Agency (AEI) under Project PID2019-109517RB-I00. ERDF funds are also acknowledged. Facilities provided by the Galician Supercomputing Centre (CESGA) are also acknowledgedS

Characterization of Hydrogels for Their Application in Tissue Regeneration

Alterations in neurogenesis result in the inevitable loss of brain nervous tissue and cause neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). In this regard, hydrogels based on natural biopolymers have attractive properties, such as excellent biocompatibility, a low immune response, and a significant similarity to the extracellular matrix (ECM) of tissues, thus supporting cell proliferation and migration. Human ECM is composed by relatively small amounts of fibrous, proteins, and polysaccharides. For example, scaffolds composed of gelatin and hyaluronic acid are highly abundant components in human ECM. The methacrylation of hyaluronic acid (HAMA) and gelatin (GelMA) through carboxyl and hydroxyl groups under UV light radiation at 365 nm produce polymeric scaffolds with elastic moduli similar to tissues, and, therefore, potential candidates to adhere, host, and facilitate cell proliferation and differentiation, which are dependent on their mechanical properties. In this work, the mechanical, thermal, and morphological properties of HAMA and GelMA hydrogel mixtures were studied and characterized via linear rheological measurements, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM)S

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presentedThis work has been funded by the Spanish Ministry of Science, Innovation and Universities (MICIU) (Grant RTI2018-095844-B-I00 and CTQ2017-88948-P), the University Complutense of Madrid (Spain) (project number UCMA05-33-010), and the Regional Government of Madrid (Grant P2018/NMT-4389). P.T. thanks Agencia Estatal de Investigación (AEI) through the Project MAT2016-80266-R and Xunta de Galicia (Grupo de Referencia Competitiva ED431C 2018/26; Agrupación Estratégica en Materiales-AEMAT ED431E 2018/08). ERDF funds are all greatly acknowledged. The proteomic analysis was performed in the Proteomics Unit of Complutense University of Madrid, a member of ProteoRed and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDFS

3D printing of a palladium-alumina cermet monolithic catalyst: catalytic evaluation in microwave-assisted cross-coupling reactions

A straightforward manufacture strategy is proposed to obtain an efficient and robust palladium-alumina (Pd0/Al2O3) cermet monolithic catalyst, specifically designed to perform safe microwave assisted organic synthesis (MAOS). In this approach, a cermet catalyst with high surface area, controlled composition and adapted shape and dimensions to a microwave reactor vessel is generated via 3D printing technology and sintering. The resulting catalyst has been explored in heterogeneous Suzuki, Sonogashira, Stille and Heck cross-coupling reactions, in MAOS. The Pd0 catalyst is permanently active, stable, without leaching and can be recycled and reused at least 200 reaction cycles. The generation of hot spots, sparking or hazardous discharges is controlled by the effective immobilization of the palladium in the monolithic structure during the reaction. The palladium content is forming part of both the internal and external structure, providing greater mechanical resistance and catalytic activity with respect to the basic ceramic material (alumina)This work was financially supported by the Consellería de Cultura, Educación e Ordenación Universitaria of the Galician Government: EM2014/022 to A.C., ED431B2016/028 to F.G. The Strategic Grouping AEMAT grant No. ED431E2018/08 and the Spanish Ministry of Science, Innovation and Universities with grant No: MAT2017-90100-C2-1-P "MA thanks Xunta de Galicia and the ERDF (ED431C 2021/21)"S

Aqueous Stable Gold Nanostar/ZIF‐8 Nanocomposites for Light‐Triggered Release of Active Cargo Inside Living Cells

This is the peer reviewed version of the following article: C. Carrillo-Carrión, R. Martínez, M. F. Navarro Poupard, B. Pelaz, E. Polo, A. Arenas-Vivo, A. Olgiati, P. Taboada, M. G. Soliman, Ú. Catalán, S. Fernández-Castillejo, R. Solà, W. J. Parak, P. Horcajada, R. A. Alvarez-Puebla, P. del Pino, Angew. Chem. Int. Ed. 2019, 58, 7078, which has been published in final form at https:// doi.org/10.1002/anie.201902817. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsA plasmonic core–shell gold nanostar/zeolitic‐imidazolate‐framework‐8 (ZIF‐8) nanocomposite was developed for the thermoplasmonic‐driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF‐8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule‐release mechanism relies on the use of near‐IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface‐enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near‐IR‐triggered cargo release inside cells, thereby leading to DNA stainingThis work has received financial support from the MINECO‐Spain (MAT2016‐80266‐R, MAT2015‐74381‐JIN, CTQ2017‐88648R, ENE2016‐79608‐C2‐1‐R, CTQ2017‐89588‐R, RYC‐2014‐15039, RYC‐2014‐16962), the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016–2019 (ED431G/09), the Agrupación Estratégica de Materiales Action (ED431E 2018/08), the Generalitat de Cataluña (2017SGR522, 2017SGR883, SLT002/16/00239), the URV (2017PFR‐URV‐B2‐02), the German Research Society (DFG PA 794‐21‐1), and the European Union (European Regional Development Fund—ERDF, H2020‐MSCA‐IF‐2016, project 749667). M.F.N.P acknowledges the CONACYT PhD fellowship programS

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.This study has been partially supported by grants from Axencia Galega de Innovación (Xunta de Galicia), the Instituto de Salud Carlos III (PI13/00292; PI14/01879), the Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS (RD12/0014), Xunta de Galicia (Consellería Educación GRC2014/027), the European Commission program FEDER and Promoting Active Ageing program: Functional Nanostructures For Alzheimer’s Disease At Ultra-Early Stages” (Pana_686009), a Research and Innovation Project, funded within the EU Horizon 2020 Programme”. Furthermore, this study was also co-funded within the POCTEP (Operational Programme for Cross-border Cooperation Spain-Portugal) program (0681_INVENNTA_1_E), co-financed by the ERDF (European Regional Development Fund). T. Sobrino (CP12/03121) and F. Campos (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III. Finally, P. Taboada thanks Mineco and Xunta de Galicia for funding through projects MAT2013-40971-R and EM2013-046, respectively. J Trekker is the recipient of an innovation grant from the IWT-VlaanderenS

Development and validation of a clinical score to estimate progression to severe or critical state in Covid-19 pneumonia hospitalized patients

The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis.Carlos III Health Institute, Spain, Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER)Instituto de Salud Carlos II