Person: López Cabarcos, Enrique
Universidad Complutense de Madrid
Faculty / Institute
Química en Ciencias Farmacéuticas
Now showing 1 - 8 of 8
PublicationOligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target Induced DNA Inter-Strand Ligand Reaction(Amer Chemical Soc., 2017-03-23) Méndez González, Diego; Laurenti, Marco; Latorre, Alfonso; Somoza, Álvaro; Vázquez, Ana; Negredo, Ana Isabel; López Cabarcos, Enrique; Calderón, Oscar Gómez; Melle Hernández, Sonia; Rubio Retama, JorgeWe present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides like miRNAs among others. The sensor is based on NaYF4:Yb,Er@SiO2 nanoparticles functionalized with ssDNA that contain azide groups on the 3' ends. In the presence of a target sequence, inter-strand ligation is possible via click-reaction between one azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As result of this specific and selective process, biotin is covalently attached to the surface of the upconversion nanoparticles. The presence of biotin on the surface of the nanoparticles allows their selective capture on a streptavidin-coated support, giving a luminescent signal proportional to the amount of target present in the test samples. With the aim of studying the analytical properties of the sensor, total RNA samples were extracted from healthy mosquitoes and spiked-in with a specific target sequence at different concentrations. The result of these experiments revealed that the sensor was able to detect 10-17 moles (100 fM) of the target sequence in mixtures containing 100 ng of total RNA per well. Similar limit of detection was found for spiked human serum samples, demonstrating its suitability for detecting specific sequences of small oligonucleotides under real conditions. By contrast, under the presence of non-complementary sequences or sequences having mismatches, the luminescent signal was negligible or conspicuously reduced. PublicationControl of upconversion luminescence by gold nanoparticle size: from quenching to enhancement(RSC, 2019-08-07) Méndez González, Diego; Melle Hernández, Sonia; Gómez Calderón, Óscar; Laurenti, Marco; Cabrera Granado, Eduardo; Egatz-Gómez, Ana; López Cabarcos, Enrique; Rubio Retama, Jorge; Díaz García, ElenaMetallic nanostructures have the potential to modify the anti-Stokes emission of upconverting nanoparticles (UCNPs) by coupling their plasmon resonance with either the excitation or the emission wavelength of the UCNPs. In this regard gold nanoparticles (AuNPs) have often been used in sensors for UCNP luminescence quenching or enhancement, although systematic studies are still needed in order to design optimal UCNP–AuNP based biosensors. Amidst mixed experimental evidence of quenching or enhancement, two key factors arise: the nanoparticle distance and nanoparticle size. In this work, we synthesize AuNPs of different sizes to assess their influence on the luminescence of UCNPs. We find that strong luminescence quenching due to resonance energy transfer is preferentially achieved for small AuNPs, peaking at an optimal size. A further increase in the AuNP size is accompanied by a reduction of luminescence quenching due to an incipient plasmonic enhancement effect. This enhancement counterbalances the luminescence quenching effect at the biggest tested AuNP size. The experimental findings are theoretically validated by studying the decay rate of the UCNP emitters near a gold nanoparticle using both a classical phenomenological model and the finite-difference time-domain method. Results from this study establish general guidelines to consider when designing sensors based on UCNPs–AuNPs as donor–quencher pairs, and suggest the potential of plasmon-induced luminescence enhancement as a sensing strategy. PublicationUltrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging(Nature Publishing Group, 2020-06-10) Santos, Harrison D. A.; Zabala Gutiérrez, Irene; Shen, Yingli; Lifante, José; Ximendes, Erving; Laurenti, Marco; Méndez González, Diego; Melle Hernández, Sonia; Gómez Calderón, Óscar; López Cabarcos, Enrique; Fernández Monsalve, Nuria; Chavez Coria, Irene; Lucena Agell, Daniel; Monge, Luis; Mackenzie, Mark D.; Marqués Hueso, José; Jones, Callum M. S.; Jacinto, Carlos; Rosal, Blanca, del; Kar, Ajoy K.; Rubio Retama, Jorge; Jaque García, DanielOptical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag2S superdots) derived from chemically synthesized Ag2S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag2S superdots enable deep-tissue in vivo imaging at low excitation intensities (<10 mW cm−2) and doses (<0.5 mg kg−1), emerging as unrivaled contrast agents for NIR-II preclinical bioimaging. These results establish an approach for developing superbright NIR-II contrast agents based on the synergy between chemical synthesis and ultrafast laser processing. PublicationMatrix tablets based on a novel poly (magnesium acrylate) hydrogel for the treatment of inflammatory bowel diseases(Elsevier, 2021-09-27) Simancas Herbada, Rebeca; Torres Suárez, Ana Isabel; Otero Espinar, Francisco; Fraguas Sánchez, Ana Isabel; López Cabarcos, Enrique; Rubio Retama, Jorge; Fernández Carballido, Ana MaríaThe objective of this work was to evaluate the potential use of a new polymer (PAMgA) in the development sustained release matrix tablets for the treatment of bowel inflammatory diseases. For this purpose, budesonide, a highly lipophilic compound, was used as model drug. Tablets with two reticulation grades of PAMgA (PAMgA 5 and 40) and with 9 mg of budesonide were developed and characterized. All the studies were carried out using biorelevant media (FaSSGF and FaSSIF). Swelling and erosion of PAMgA tablets was influenced by the reticulation grade of the polymer and the biorelevant media assayed, being water uptake higher for PAMgA 40 tablets in intestinal fluid, whereas PAMgA 5 showed more intense erosion in this biorelevant medium. Budesonide was released slowly from PAMgA tablets, both in gastric and intestinal environment, following Super case II transport kinetics (relaxation-controlled delivery), with a lag time of around 1–2 h. When the dissolution medium was changed sequentially throughout the trial, 75% of the budesonide dose was released in a sustained manner between 4 and 20 h of testing from PAMgA tablets, showing a more controlled budesonide release than Entocort® and Budenofalk® (commercially available sustained release formulations of budesonide). In conclusion, PAMgA polymer allows controlling the release of highly lipophilic drugs as budesonide, being an useful excipient for the development of sustained release matrix tablets. PublicationFRET distance dependence from upconverting nanoparticles to quantum dots(Amer Chemical Soc, 2018-05) Melle Hernández, Sonia; Gómez Calderón, Óscar; Laurenti, Marco; Méndez González, Diego; Egatz-Gómez, Ana; López Cabarcos, Enrique; Cabrera Granado, Eduardo; Díaz García, Elena; Rubio Retama, JorgeFörster resonant energy transfer (FRET) with upconverting nanoparticles (UCNPs) as donors and quantum dots (QDs) as acceptors has been regarded as a promising tool for biosensing applications. In this work, we use time-resolved fluorescence spectroscopy to analyze the UCNP-to-QD FRET and we focus on the most relevant parameter of the FRET phenomenon, UCNP-QD distance. This distance is controlled by a nanometric silica shell around the UCNP surface. We theoretically reproduce the experimental results applying FRET theory to the distribution of emitting erbium ions in the UCNP. This simple model allows us to estimate the contribution of every erbium ion to the final FRET response and to explore different strategies to improve FRET efficiency. PublicationThe effects of dopant concentration and excitation intensity on the upconversion and downconversion emission processes of β-NaYF4:Yb3+,Er3+nanoparticles(Royal Soc. Chemistry, 2021-06-04) Torres Vera, Vivian; Méndez González, Diego; Ramos Ramos, D.J.; Igalla El Youssfi, Asmae; Laurenti, Marco; Contreras Cáceres, Rafael; López Cabarcos, Enrique; Díaz García, Elena; Rubio Retama, Jorge; Melle Hernández, Sonia; Gómez Calderón, OscarThe dopant concentration of lanthanide ions in photon upconversion nanoparticles (UCNPs) remains one of the key points to boost the brightness of these nanomaterials and, therefore, their application developments. Here, we analyzed the effect of Er3+ and Yb3+ dopant concentrations of b-NaYF4:Yb3+,Er3+ nanoparticles on the visible upconversion and near-infrared downconversion luminescence intensities. Our approach carefully excluded all other factors whose variation affects luminescence properties such as the size, morphology, crystal structure, ion distribution, ligand, and surrounding medium, allowing us to exactly infer the influence of the ratio of Yb3+ to Er3+ ions on the nanoparticle luminescence. To maintain the size and morphological properties of nanoparticles, we used a total dopant concentration of 22% while varying the ratio of Yb3+ to Er3+ ions from 0 to 10. A huge increase in luminescence takes place as the Yb/Er ratio increases following a power-law behavior, and this luminescence enhancement is greater at low excitation intensities. Above a Yb/Er ratio of around two, saturation occurs with a slight peak when this ratio is around four. Simulations using a rate equation model showed that upconversion luminescence (UCL) is mainly produced by the energy transfer between neighboring Er3+ ions at low Yb/Er ratios, while at high ratios, the energy transfer from Yb3+ to Er3+ ions dominates. However, downconversion luminescence (DCL) is produced at all analyzed ratios, except 0, by the previous mechanism. PublicationContribution of resonance energy transfer to the luminescence quenching of upconversion nanoparticles with graphene oxide(Academic Press Inc Elsevier Science, 2020-04-20) Méndez González, Diego; Gómez Calderón, Óscar; Melle Hernández, Sonia; González Izquierdo, Jesús; Bañares Morcillo, Luis; López Díaz, David; Velazquez Salicio, M. Mercedes; López Cabarcos, Enrique; Rubio Retama, Jorge; Laurenti, MarcoUpconversion nanoparticles (UCNP) are increasingly used due to their advantages over conventional fluorophores, and their use as resonance energy transfer (RET) donors has permitted their application as biosensors when they are combined with appropriate RET acceptors such as graphene oxide (GO). However, there is a lack of knowledge about the design and influence that GO composition produces over the quenching of these nanoparticles that in turn will define their performance as sensors. In this work, we have analysed the total quenching efficiency, as well as the actual values corresponding to the RET process between UCNPs and GO sheets with three different chemical compositions. Our findings indicate that excitation and emission absorption by GO sheets are the major contributor to the observed luminescence quenching in these systems. This challenges the general assumption that UCNPs luminescence deactivation by GO is caused by RET. Furthermore, RET efficiency has been theoretically calculated by means of a semiclassical model considering the different nonradiative energy transfer rates from each Er3+ ion to the GO thin film. These theoretical results highlight the relevance of the relative positions of the Er3+ ions inside the UCNP with respect to the GO sheet in order to explain the RET-induced efficiency measurements. PublicationControlled Release of Highly Hydrophilic Drugs from Novel Poly(Magnesium Acrylate) Matrix Tablets(MDPI, 2020-02-19) Simancas Herbada, Rebeca; Fernández Carballido, Ana María; Aparicio Blanco, Juan; Slowing Barillas, Karla Verónica; Rubio Retama, Jorge; López Cabarcos, Enrique; Torres Suárez, Ana IsabelThe potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two di_erent crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel e_ectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its di_usion through the gel layer (Fickian di_usion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.