A Quantum Dot-Based FLIM Glucose Nanosensor

In the last few years, quantum dot (QD) nanoparticles have been employed for bioimaging and sensing due to their excellent optical features. Most studies have used photoluminescence (PL) intensity-based techniques, which have some drawbacks, especially when working with nanoparticles in intracellular media, such as fluctuations in the excitation power, fluorophore concentration dependence, or interference from cell autofluorescence. Some of those limitations can be overcome with the use of time-resolved spectroscopy and fluorescence lifetime imaging microscopy (FLIM) techniques. In this work, CdSe/ZnS QDs with long decay times were modified with aminophenylboronic acid (APBA) to achieve QD-APBA conjugates, which can act as glucose nanosensors. The attachment of the boronic acid moiety on the surface of the nanoparticle quenched the PL average lifetime of the QDs. When glucose bonded to the boronic acid, the PL was recovered and its lifetime was enhanced. The nanosensors were satisfactorily applied to the detection of glucose into MDA-MB-231 cells with FLIM. The long PL lifetimes of the QD nanoparticles made them easily discernible from cell autofluorescence, thereby improving selectivity in their sensing applications. Since the intracellular levels of glucose are related to the metabolic status of cancer cells, the proposed nanosensors could potentially be used in cancer diagnosis.This research was funded by grants CTQ2014-56370-R and CTQ2017-85658-R from the Spanish Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (AEI), and the European Regional Development Fund (ERDF)

Evaluation of heteroscorpionate ligands as scaffolds for the generation of Ruthenium(II) metallodrugs in breast cancer therapy

The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of heteroscorpionate-based ruthenium derivatives was synthesized, characterized, and evaluated as an alternative to platinum therapy for breast cancer therapy. In vitro, the antitumoral activity of the novel derivatives was assessed in a series of breast cancer cell lines using UNICAM-1 and cisplatin as metallodrug control. Through this approach, a bimetallic heteroscorpionate-based metallodrug (RUSCO-2) was identified as the lead compound of the series with an IC50 value range as low as 3–5 μM. Notably, RUSCO-2 was found to be highly cytotoxic in TNBC cell lines, suggesting a mode of action independent of the receptor status of the cells. As a proof of concept and taking advantage of the luminescent properties of one of the complexes obtained, uptake was monitored in human breast cancer MCF7 cell lines by fluorescence lifetime imaging microscopy (FLIM) to reveal that the compound is evenly distributed in the cytoplasm and that the incorporation of the heteroscorpionate ligand protects it from aqueous processes, conversion in another entity, or the loss of the chloride group. Finally, ROS studies were conducted, lipophilicity was estimated, the chloride/water exchange was studied, and stability studies in simulated biological media were carried out to propose structure-activity relationships.Ministerio de Ciencia e Innovación y Agencia Estatal de la Investigación, Spain (grants CPP2021-008597, PID2020-117788RB-I00 and RED2022-134287-T funded by MCIN/AEI/10.13039/501100011033)Grants SBPLY/21/180501/000050 and SBPLY/21/180501/000132 funded by JCCM and by EU through Fondo Europeo de Desarrollo RegionalGrant 2021-GRIN-31240 funded by Universidad de Castilla-La ManchaInstituto de Salud Carlos III (grant number PI16/01121)Instituto de Salud Carlos III (ISCIII, PI19/00808)ACEPAIN foundationAFANIONJunta de Comunidades de Castilla-La Mancha for Postdoctoral fellowship (2018/15132)University of Castilla-La Mancha for Predoctoral fellowship (2020-PREDUCLM-16603

Mitochondrial pH Nanosensors for Metabolic Profiling of Breast Cancer Cell Lines

We thank the company Nanogetic S.L. (Granada, Spain) for support with the synthesis of the SS peptides and the Centro de Instrumentacion Cientifica (CIC) of the Universidad de Granada for use of the TEM facilities.The main role of mitochondria, as pivotal organelles for cellular metabolism, is the production of energy (ATP) through an oxidative phosphorylation system. During this process, the electron transport chain creates a proton gradient that drives the synthesis of ATP. One of the main features of tumoral cells is their altered metabolism, providing alternative routes to enhance proliferation and survival. Hence, it is of utmost importance to understand the relationship between mitochondrial pH, tumoral metabolism, and cancer. In this manuscript, we develop a highly specific nanosensor to accurately measure the intramitochondrial pH using fluorescence lifetime imaging microscopy (FLIM). Importantly, we have applied this nanosensor to establish differences that may be hallmarks of different metabolic pathways in breast cancer cell models, leading to the characterization of different metabophenotypes.Spanish Ministerio de Ciencia, Innovacion y Universidades CTQ2014-56370-R CTQ2017-86568-REuropean Union (EU)Spanish Agencia Estatal de InvestigacionFundacion Ramon Arece

Simple and non-charged long-lived fluorescent intracellular organelle trackers

In this work we evaluated by FLIM microscopy the preferential accumulation of long-lived acridone derivatives in mitochondria and lysosomes, based on a new concept of non-protonable and non-charged groups carriers. Thus, thiophene ring has been proved to act as mithocondria carrier whereas pyridine derivative is preferentially accumulated into lisosomes.Ministerio de Economía y Competitividad for funding (CTQ2017-85454-C2-1-P and CTQ2017-85658-R).Junta de AndalucíaMinisterio de Economía y Competitivida

Intracellular Zn2+ detection with quantum dot-based FLIM nanosensors

Fluorescence Lifetime Imaging Microscopy (FLIM) has been employed for the detection of intracellular Zn2+ levels, implicated in various signalling pathways, using a family of quantum dot (QD) nanosensors. The sensing mechanism was based on photoinduced electron transfer (PET) between an azacycle receptor group and the QD nanoparticles.This work was supported by Fundación Ramon Areces and grant CTQ2014-56370-R from Ministerio de Economia y Competitividad of Spain

Historia de las Antillas (volumen 1)

Peer reviewe

Slavery and the african cultural legacy in the Caribbean

Con autorización de la editorial para este libro.[EN] The purpose of this book is to raise awareness among a wide audience of one of the most significant and shameful phenomena for humanity, as was the enslavement of over twelve and a half million Africans who were brought to America and forced to work and live as slaves. Many countries participated in the slave trade at different times and withvaried intensity (Great Britain, Portugal, France, Spain, Denmark, Netherlands, Germany, United States...).[ES] El propósito de esta obra es dar a conocer a un público amplio uno de los fenómenos de mayor trascendencia y vergüenza para la humanidad como fue la esclavización de más de doce millones y medio de africanos que fueron trasladados a América, obligados a trabajar y vivir como esclavos. Muchos países participaron en la trata de esclavos en distintos momentos y con diferente intensidad (Gran Bretaña, Portugal, Francia, España, Dinamarca, Países Bajos, Alemania, Estados Unidos…).Connected Worlds: The Caribbean, Origin of Modern World. This project has received funding from the European Union´s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement Nº 823846. This project is directed by professor Consuelo Naranjo Orovio, Institute of History-CSIC.Peer reviewe