Dual Role of Subphthalocyanine Dyes for Optical Imaging and Therapy of Cancer

This is the peer-reviewed version of the following article: van de Winckel, E., Mascaraque, M., Zamarrón, A., Juarranz de la Fuente, Á., Torres, T., & de la Escosura, A. (2018). Dual role of subphthalocyanine dyes for optical imaging and therapy of cancer. Advanced Functional Materials, 28(24), 1705938., which has been published in final form at https://doi.org/10.1002/adfm.201705938. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingThe family of subphthalocyanine (SubPc) macrocycles represents an interesting class of nonplanar aromatic dyes with promising features for energy conversion and optoelectronics. The use of SubPcs in biomedical research is, on the contrary, clearly underexplored, despite their documented high fluorescence and singlet oxygen quantum yields. Herein, for the first time it is shown that the interaction of these chromophores with light can also be useful for theranostic applications, which in the case of SubPcs comprise optical imaging and photodynamic therapy (PDT). In particular, the article evaluates, through a complete in vitro study, the dual-role capacity of a novel series of SubPcs as fluorescent probes and PDT agents, where the macrocycle axial substitution determines their biological activity. The 2D and 3D imaging of various cancer cell lines (i.e., HeLa, SCC-13, and A431) has revealed, for example, different subcellular localization of the studied photosensitizers (PS), depending on the axial substituent they bear. These results also show excellent photocytotoxicities, which are affected by the PS localization. With the best dual-role PS, preliminary in vivo studies have demonstrated their therapeutic potential. Overall, the present paper sets the bases for an unprecedented biomedical use of these well-known optoelectronic materials.E.v.d.W. and M.M. contributed equally to this work. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Program FP7‐PEOPLE‐2012‐ITN under REA grant agreement No. GA 316975. AdlE holds a Ramón y Cajal contract from the Spanish Ministry of Economy (MINECO). This work was supported by EU (CosmoPHOS‐nano, FP7‐NMP‐2012‐6, 310337‐2; GLOBASOL, FP7‐ENERGY‐2012‐J, 309194‐2), the Spanish MINECO (CTQ‐2014‐52869‐P (TT) and CTQ‐2014‐53673‐P (AdlE)), CAM (FOTOCARBON, S2013/MIT‐2841), grants from Instituto de Salud Carlos III, MINECO and Feder Funds (PI15/00974) and by S2010/BMD‐2359 from Comunidad de Madrid

Raman and Fluorescence Enhancement Approaches in Graphene-Based Platforms for Optical Sensing and Imaging

This article belongs to the Special Issue Physics and Chemistry of Graphene: From Fundamentals to Applications.The search for novel platforms and metamaterials for the enhancement of optical and particularly Raman signals is still an objective since optical techniques offer affordable, noninvasive methods with high spatial resolution and penetration depth adequate to detect and image a large variety of systems, from 2D materials to molecules in complex media and tissues. Definitely, plasmonic materials produce the most efficient enhancement through the surface-enhanced Raman scattering (SERS) process, allowing single-molecule detection, and are the most studied ones. Here we focus on less explored aspects of SERS such as the role of the inter-nanoparticle (NP) distance and the ultra-small NP size limit (down to a few nm) and on novel approaches involving graphene and graphene-related materials. The issues on reproducibility and homogeneity for the quantification of the probe molecules will also be discussed. Other light enhancement mechanisms, in particular resonant and interference Raman scatterings, as well as the platforms that allow combining several of them, are presented in this review with a special focus on the possibilities that graphene offers for the design and fabrication of novel architectures. Recent fluorescence enhancement platforms and strategies, so important for bio-detection and imaging, are reviewed as well as the relevance of graphene oxide and graphene/carbon nanodots in the field.The research leading to these results has received funding from Ministerio de Ciencia e Innovación (RTI2018-096918-B-C41). S.C. acknowledges the grant BES-2016-076440 from MINECO

Microscopic dynamics of glycerol in its crystalline and glassy states

9 págs.; 6 figs.; 1 tab.The dynamics of crystalline glycerol are studied by means of Raman spectroscopy and lattice dynamics calculations employing a semiflexible model to represent the low-lying molecular vibrations. The latter is validated against structural, thermodynamic, and spectroscopic data. The results serve to set an absolute frequency scale for glassy glycerol, which is also studied by Raman and incoherent inelastic-neutron scattering. Some implications of the present findings regarding ensuing discussions on glassy dynamics are finally commented on. ©1996 American Physical SocietyThis work has been supported in part by DGICYT Grant No. PB92- 0114-C04.Peer Reviewe

Short Synthesis of Novel Recyclable Chiral Bifunctional Thioureas from Aminoalkyl Polystyrene and their use as Organocatalysts in Stereoselective aza-Henry Reaction

Producción CientíficaA series of supported bifunctional thioureas has been prepared, in one or two steps, from commercially available aminoalkyl polystyrene resins. They differ in the length of the tether attaching the thiourea to the polymer chain, and the nature of the amino thiourea component. All the materials are able to promote stereoselective aza-Henry reaction with very good stereoselection, and they can be recycled maintaining the catalytic activity.Ministerio de Economía, Industria y Competitividad (CTQ2014-59870-P)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA064U13

Breast cancer biomarker detection through the photoluminescence of epitaxial monolayer MoS2 fakes

The following article appeared in Scientific Reports 10 (2020): 16039 and may be found at https://www.nature.com/articles/s41598-020-73029-9In this work we report on the characterization and biological functionalization of 2D MoS2 fakes, epitaxially grown on sapphire, to develop an optical biosensor for the breast cancer biomarker miRNA21. The MoS2 fakes were modifed with a thiolated DNA probe complementary to the target biomarker. Based on the photoluminescence of MoS2, the hybridization events were analyzed for the target (miRNA21c) and the control non-complementary sequence (miRNA21nc). A specifc redshift was observed for the hybridization with miRNA21c, but not for the control, demonstrating the biomarker recognition via PL. The homogeneity of these MoS2 platforms was verifed with microscopic maps. The detailed spectroscopic analysis of the spectra reveals changes in the trion to excitation ratio, being the redshift after the hybridization ascribed to both peaks. The results demonstrate the benefts of optical biosensors based on MoS2 monolayer for future commercial devicesThe research is supported by the MINECO (CTQ2017-84309-C2-2-R, CTQ2017-84309-C2-1-R, ELECTROBIONET, RED2018-102412-T) and Comunidad de Madrid (TRANSNANOAVANSENS, P2018/NMT4349) projects. ARC acknowledges Ramón y Cajal program (under contract number RYC-2015-18047

Effect of Pristine Graphene on Methylammonium Lead Iodide Films and Implications on Solar Cell Performance

The relatively low stability of solar cells based on hybrid halide perovskites is the main issue to be solved for the implementation in real life of these extraordinary materials. Degradation is accelerated by temperature, moisture, oxygen, and light and mediated by halide easy hopping. The approach here is to incorporate pristine graphene, which is hydrophobic and impermeable to gases and likely limits ionic diffusion while maintaining adequate electronic conductivity. Low concentrations of few-layer graphene platelets (up to 24 × 10–3 wt %) were incorporated to MAPbI3 films for a detailed structural, optical, and transport study whose results are then used to fabricate solar cells with graphene-doped active layers. The lowest graphene content delays the degradation of films with time and light irradiation and leads to enhanced photovoltaic performance and stability of the solar cells, with relative improvement over devices without graphene of 15% in the power conversion efficiency, PCE. A higher graphene content further stabilizes the perovskite films but is detrimental for in-operation devices. A trade-off between the possible sealing effect of the perovskite grains by graphene, that limits ionic diffusion, and the reduction of the crystalline domain size that reduces electronic transport, and, especially, the detected increase of film porosity, that facilitates the access to atmospheric gases, is proposed to be at the origin of the observed trends. This work demonstrated how the synergy between these materials can help to develop cost-effective routes to overcome the stability barrier of metal halide perovskites, introducing active layer design strategies that allow commercialization to take off.We acknowledge financial support by the Spanish Ministry of Science and Innovation under Projects PID2020-115514RB-I00 (C.C.), MAT2015-65356-C3-2-R (A.A), and PID2019-107314RB-I00 (I.M-S). This work was partially supported by European Research Council (ERC) via Consolidator Grant (724424-No-LIMIT) (I.M-S), AYUDA PUENTE 2020 URJC (C.C.). Associated Lab LABCADIO belonging to Community of Madrid, CM, net laboratories ref 351 is also acknowledged (C.C.). T.S.R. acknowledges funding from CM and European Social Fund (ESF) under the Talento fellowship 2017-T2/IND-5586 and project F660 financed by CM and Rey Juan Carlos University under action 1, “Encouragement of Young Phd students investigation". C.R-O. acknowledges funding from the Spanish Ministry of Science and Innovation under a FPI predoctoral contract (PRE2019-088433)

Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival

et al.Sos1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases. The embryonic lethality of Sos1 null mutants has hampered ascertaining the specific in vivo contributions of Sos1 and Sos2 to processes controlling adult organism survival or development of hematopoietic and nonhematopoietic organs, tissues, and cell lineages. Here, we generated a tamoxifen-inducible Sos1-null mouse strain allowing analysis of the combined disruption of Sos1 and Sos2 (Sos1/2) during adulthood. Sos1/2 double-knockout (DKO) animals died precipitously, whereas individual Sos1 and Sos2 knockout (KO) mice were perfectly viable. A reduced percentage of total bone marrow precursors occurred in single-KO animals, but a dramatic depletion of B-cell progenitors was specifically detected in Sos1/2 DKO mice. We also confirmed a dominant role of Sos1 over Sos2 in early thymocyte maturation, with almost complete thymus disappearance and dramatically higher reduction of absolute thymocyte counts in Sos1/2 DKO animals. Absolute counts of mature B and T cells in spleen and peripheral blood were unchanged in single-KO mutants, while significantly reduced in Sos1/2 DKO mice. Our data demonstrate functional redundancy between Sos1 and Sos2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes.Work was supported by grants FIS-PS09/01979, RTICC-RD12/0036/0001, and RD12/0036/0048 from Instituto de Salud Carlos III (Madrid, Spain) and Fundación Samuel Solórzano (Salamanca, Spain). This research was also supported by the Intramural Research Program of the CCR, NCI, NIH.Peer Reviewe

Grain selective Cu oxidation and anomalous shift of graphene 2D Raman peak in the graphene-Cu system

Understanding the interaction between graphene and its supporting substrate is of paramount importance for the development of graphene based applications. In this work the interplay of the technologically relevant graphene-Cu system is investigated in detail as a function of substrate grain orientation in Cu polycrystalline foils. While (100) and (111) Cu grains show the well-known graphene-enhanced oxidation, (110) grains present a superior oxidation resistance compared to uncovered Cu and an anomalous shift of its graphene 2D Raman band which cannot be explained by the known effects of strain and doping. These results are interpreted in terms of a weak graphene-Cu coupling at the (110) grains, and show that graphene can actually be used as anticorrosion coating, contrary to previously reported. The anomalous shift is suggested to be the result of an enhanced outer Raman scattering process which surpasses the usually dominant inner process. Since Raman spectroscopy is widely used as first and main characterization tool of graphene, the existence of an anomalous shift on its 2D band not only challenges the current theory of Raman scattering in graphene, but also has profound implications from an experimental point of view

Epigenetic features of human telomeres

Although subtelomeric regions in humans are heterochromatic, the epigenetic nature of human telomeres remains controversial. This controversy might have been influenced by the confounding effect of subtelomeric regions and interstitial telomeric sequences (ITSs) on telomeric chromatin structure analyses. In addition, different human cell lines might carry diverse epigenetic marks at telomeres. We have developed a reliable procedure to study the chromatin structure of human telomeres independently of subtelomeres and ITSs. This procedure is based on the statistical analysis of multiple ChIP-seq experiments. We have found that human telomeres are not enriched in the heterochromatic H3K9me3 mark in most of the common laboratory cell lines, including embryonic stem cells. Instead, they are labeled with H4K20me1 and H3K27ac, which might be established by p300. These results together with previously published data argue that subtelomeric heterochromatin might control human telomere functions. Interestingly, U2OS cells that exhibit alternative lengthening of telomeres have heterochromatic levels of H3K9me3 in their telomeres.Ministerio de Economía, Industria y Competitividad de España BIO2016–78955-PConsejo Europeo de Investigación ERC2014 AdG669898 TARLOOPMinisterio de Economía y Competitividad de España BFU2016–75058-

Uso estuarial y composición de las especies de peces en el sub-estuario Solís Grande, Uruguay

A total of 1,298 fish representing estuarine, freshwater, marine migrants, anadromous and catadromous species were caught. Dominance of postlarvae and juveniles was observed. Mugil liza was the most abundant species. Jenynsia multidentata, Pogonias cromis and Cyprinus carpio were new records of species for the Solís Grande sub-estuary.Fueron capturados un total de 1.298 peces, representando especies estuariales, dulciacuícolas, marino migrantes, anádromas y catádromas. Fue observada una dominancia de post-larvas y juveniles. Mugil liza fue la especie más abundante. Jenynsia multidentata, Pogonias cromis y Cyprinus carpio fueron nuevos registros de especies en el subestuario Solís Grande