Person:
Filice, Marco

First Name

Marco

Last Name

Filice

URI

https://hdl.handle.net/20.500.14352/86197

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Orgánica

Identifiers

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Search Results

Now showing 1 - 10 of 14

Applications of Nanomaterials Based on Magnetite and Mesoporous Silica on the Selective Detection of Zinc Ion in Live Cell Imaging
(Nanomaterials, 2018) Erami, Roghayeh Sadeghi; Ovejero, Karina; Meghdadi, Soraia; Filice, Marco; Amirnasr, Mehdi; Rodríguez Diéguez, Antonio; Orden, María Ulagares de la; Gómez Ruiz, Santiago
Functionalized magnetite nanoparticles (FMNPs) and functionalized mesoporous silica nanoparticles (FMSNs) were synthesized by the conjugation of magnetite and mesoporous silica with the small and fluorogenic benzothiazole ligand, that is, 2(2-hydroxyphenyl)benzothiazole (hpbtz). The synthesized fluorescent nanoparticles were characterized by FTIR, XRD, XRF, 13C CP MAS NMR, BET, and TEM. The photophysical behavior of FMNPs and FMSNs in ethanol was studied using fluorescence spectroscopy. The modification of magnetite and silica scaffolds with the highly fluorescent benzothiazole ligand enabled the nanoparticles to be used as selective and sensitive optical probes for zinc ion detection. Moreover, the presence of hpbtz in FMNPs and FMSNs induced efficient cell viability and zinc ion uptake, with desirable signaling in the normal human kidney epithelial (Hek293) cell line. The significant viability of FMNPs and FMSNs (80% and 92%, respectively) indicates a potential applicability of these nanoparticles as in vitro imaging agents. The calculated limit of detections (LODs) were found to be 2.53 × 10−6 and 2.55 × 10−6 M for Fe3O4-H@hpbtz and MSN-Et3N-IPTMS-hpbtz-f1, respectively. FMSNs showed more pronounced zinc signaling relative to FMNPs, as a result of the more efficient penetration into the cells.
Modulation of the Catalytic Properties of Lipase B from Candida antarctica by Immobilization on Tailor-Made Magnetic Iron Oxide Nanoparticles: The Key Role of Nanocarrier Surface Engineering
(Polymers, 2018) Viñambres, Mario; Filice, Marco; Marciello, Marzia
The immobilization of biocatalysts on magnetic nanomaterial surface is a very attractive alternative to achieve enzyme nanoderivatives with highly improved properties. The combination between the careful tailoring of nanocarrier surfaces and the site-specific chemical modification of biomacromolecules is a crucial parameter to finely modulate the catalytic behavior of the biocatalyst. In this work, a useful strategy to immobilize chemically aminated lipase B from Candida antárctica on magnetic iron oxide nanoparticles (IONPs) by covalent multipoint attachment or hydrophobic physical adsorption upon previous tailored engineering of nanocarriers with poly-carboxylic groups (citric acid or succinic anhydride, CALBEDA@CA-NPs and CALBEDA@SA-NPs respectively) or hydrophobic layer (oleic acid, CALBEDA@OA-NPs) is described. After full characterization, the nanocatalysts have been assessed in the enantioselective kinetic resolution of racemic methyl mandelate. Depending on the immobilization strategy, each enzymatic nanoderivative permitted to selectively improve a specific property of the biocatalyst. In general, all the immobilization protocols permitted loading from good to high lipase amount (149 < immobilized lipase < 234 mg/gFe). The hydrophobic CALBEDA@OA-NPs was the most active nanocatalyst, whereas the covalent CALBEDA@CA-NPs and CALBEDA@SA-NPs were revealed to be the most thermostable and also the most enantioselective ones in the kinetic resolution reaction (almost 90% ee R-enantiomer). A strategy to maintain all these properties in long-time storage (up to 1 month) by freeze-drying was also optimized. Therefore, the nanocarrier surface engineering is demonstrated to be a key-parameter in the design and preparation of lipase libraries with enhanced catalytic properties.
Hybrid Decorated Core@Shell Janus Nanoparticles as a Flexible Platform for Targeted Multimodal Molecular Bioimaging of Cancer
(ACS Applied Materials & Interfaces, 2018) Sánchez, Alfredo; Ovejero Paredes, Karina; Ruiz-Cabello, Jesús; Martínez Ruiz, María Paloma; Pingarrón Carrazón, José Manuel; Villalonga Santana, Reynaldo; Filice, Marco
In the recent years, targeted cancer theranosis, the concomitant therapeutic treatment and selective visualization of cancerous tissue, has become a powerful strategy to improve patient prognosis. In this context, targeted multimodal molecular imaging, the combination of different imaging modalities overcoming their individual limitations, has attracted great attention. Due to their unique properties, advanced nanomaterials have taken center stage in the development of theranostics. In this work, we report a novel Janus nanoplatform by combining an Fe3O4 NPs/mesoporous silica core@shell face together with an Au nanoparticle face. Due to its anisotropy, this hybrid nanomaterial enabled the orthogonal site-selective modification of each face permitting the incorporation of a targeting peptide for cancer detection (cRGD) and a fluorescent dye. Due to the intrinsic characteristics of this Janus nanoplatform together with those selectively generated on their surfaces, the resulting hybrid nanocarrier successfully promoted the in vivo tumor-targeted multimodal imaging by magnetic resonance (Fe3O4 core), computed tomography (AuNP face), and fluorescent tracking (fluorescent dye loading) in a fibrosarcoma-bearing mouse model. The achieved results endorse these hybrid Janus nanoparticles as a powerful and flexible platform with integrated imaging and carrier functionalities to be equipped with therapeutic features to generate an advanced multifunctional nanocarrier for targeted cancer theranosis.
Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer
(Cancers, 2020) Ovejero Paredes, Karina; Díaz García, Diana; García Almodóvar, Victoria; Lozano Chamizo, Laura; Marciello, Marzia; Díaz-Sánchez, Miguel; Prashar, Sanjiv; Gómez-Ruiz, Santiago; Filice, Marco
Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph3Sn{SCH2CH2CH2Si(OMe)3} (MSN-AP-Sn), a folate fragment (MSN-AP-FA-Sn), and an enzyme-responsive peptide able to release the metallodrug only inside cancer cells (MSN-AP-FA-PEP-S-Sn), have been synthesized and fully characterized by applying physico-chemical techniques. After that, an in vitro deep determination of the therapeutic potential of the achieved multifunctional nanovectors was carried out. The results showed a high cytotoxic potential of the MSN-AP-FA-PEP-S-Sn material against triple negative breast cancer cell line (MDA-MB-231). Moreover, a dose-dependent metallodrug-related inhibitory effect on the migration mechanism of MDA-MB-231 tumor cells was shown. Subsequently, the organotin-functionalized nanosystems have been further modified with the NIR imaging agent Alexa Fluor 647 to give three different theranostic silica-based nanoplatforms, namely, MSN-AP-Sn-AX (AX-1), MSN-AP-FA-Sn-AX (AX-2), and MSN-AP-FA-PEP-S-Sn-AX (AX-3). Their in vivo potential as theranostic markers was further evaluated in a xenograft mouse model of human breast adenocarcinoma. Owing to the combination of the receptor-mediated site targeting and the specific fine-tuned release mechanism of the organotin metallodrug, the nanotheranostic drug MSN-AP-FA-PEP-S-Sn-AX (AX-3) has shown targeted diagnostic ability in combination with enhanced therapeutic activity by promoting the inhibition of tumor growth with reduced hepatic and renal toxicity upon the repeated administration of the multifunctional nanodrug.
Fine Modulation of the Catalytic Properties of Rhizomucor miehei Lipase Driven by Different Immobilization Strategies for the Selective Hydrolysis of Fish Oil
(Molecules, 2020) Yousefi, Maryam; Marciello, Marzia; Guisan, José Manuel; Fernandez-Lorente, Gloria; Mohammadi, Mehdi; Filice, Marco
Functional properties of each enzyme strictly depend on immobilization protocol used for linking enzyme and carrier. Different strategies were applied to prepare the immobilized derivatives of Rhizomucor miehei lipase (RML) and chemically aminated RML (NH2-RML). Both RML and NH2-RML forms were covalently immobilized on glyoxyl sepharose (Gx-RML and GxNH2-RML), glyoxyl sepharose dithiothreitol (Gx-DTT-RML and Gx-DTT-NH2-RML), activated sepharose with cyanogen bromide (CNBr-RML and CNBr-NH2-RML) and heterofunctional epoxy support partially modified with iminodiacetic acid (epoxy IDA-RML and epoxy-IDA-NH2-RML). Immobilization varied from 11% up to 88% yields producing specific activities ranging from 0.5 up to 1.9 UI/mg. Great improvement in thermal stability for Gx-DTT-NH2-RML and epoxy-IDA-NH2-RML derivatives was obtained by retaining 49% and 37% of their initial activities at 70 ◦C, respectively. The regioselectivity of each derivative was also examined in hydrolysis of fish oil at three different conditions. All the derivatives were selective between cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) in favor of EPA. The highest selectivity (32.9 folds) was observed for epoxy-IDA-NH2-RML derivative in the hydrolysis reaction performed at pH 5 and 4 ◦C. Recyclability study showed good capability of the immobilized biocatalysts to be used repeatedly, retaining 50–91% of their initial activities after five cycles of the reaction.
Useful Oriented Immobilization of Antibodies on Chimeric Magnetic Particles: Direct Correlation of Biomacromolecule Orientation with Biological Activity by AFM Studies
(Langmuir, 2014) Marciello, Marzia; Filice, Marco; Olea, David; Velez, Marisela; Guisan, José M.; Mateo, César
The preparation and performance of a suitable chimeric biosensor basedon antibodies (Abs) immobilized on lipase-coated magnetic particles by means of astanding orienting strategy are presented. This novel system is based on hydrophobicmagnetic particles coated with modified lipase molecules able to orient and furtherimmobilize different Abs in a covalent way without any previous site-selective chemicalmodification of biomacromolecules. Different key parameters attending the process werestudied and optimized. The optimal preparation was performed using a controlled loading(1 nmol Ab g−1chimeric support) at pH 9 and a short reaction time to recover abiological activity of about 80%. AFM microscopy was used to study and confirm the Abs-oriented immobilization on lipase-coated magnetic particles and thefinal achievement of ahighly active and recyclable chimeric immune sensor. This direct technique wasdemonstrated to be a powerful alternative to the indirect immunoactivity assay methodsfor the study of biomacromolecule-oriented immobilizations.
Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines
(Pharmaceutics, 2020) Díaz-García, Diana; Montalbán-Hernández, Karla; Mena-Palomo, Irene; Achimas-Cadariu, Patriciu; Rodríguez Diéguez, Antonio; Eduardo, López-Collado; Prashar, Sanjiv; Ovejero Paredes, Karina; Filice, Marco; Fischer-Fodor, Eva; Gómez-Ruiz, Santiago
The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors.
Project number: 270
Jugando con métodos interactivos para incentivar el aprendizaje de la física y fisicoquímica
(2023) Marciello, Marzia; Alvear Jiménez, Alexis Fernando; Contreras Cáceres, Rafael; Díaz García, Diana; Fernández Fernández, María De La Cabeza; Filice, Marco; García Almodóvar, Victoria; Gómez Ruiz, Santiago; Laurenti, Marco; Lozano Chamizo, Laura; Méndez González, Diego; Ovejero Paredes, Karina; Sánchez Sánchez, Visitación
La sociedad actual se presenta cada día más tecnificada y los estudiantes están creciendo en ella desarrollando distintas capacidades cognitivas que resultan casi imprescindible comprender y atender para poder aumentar su interés en el aprendizaje de diferentes temas. Esta realidad está llevando los profesores a reconfigurar sus estrategias pedagógicas, actualizando los métodos educativos con el fin de mejorar la calidad de la educación adaptando los contenidos que se imparten con las necesidades de la sociedad. Por ello, cada vez es más frecuente recurrir a nuevas herramientas como las TIC (Tecnologías de la Información y las Comunicaciones) y a aplicaciones lúdicas que apoyen y fomenten el proceso de aprendizaje. La aplicación de las TICs en la enseñanza, ha supuesto un avance en la transmisión y recepción del conocimiento para incentivar a los alumnos al aprendizaje de aquellas asignaturas que suponen una mayor dificultad durante su proceso formativo. Asimismo, la gamificación, que consiste en incorporar elementos de juegos como las recompensas y la competición para animar a las estudiantes a realizar tareas que normalmente se consideran aburridas, está ganando cada día más atención sobre todo gracias a su innegable carácter motivacional. De hecho, el juego es un activador en la atención y surge como alternativa para complementar los esquemas de la enseñanza tradicional. Debido a su naturaleza intrínseca, el aprendizaje de la física y de la fisicoquímica (tanto en campo farmacéutico como en general) suele resultar un proceso complicado y muchas veces difícil de entender. Los métodos tradicionales de enseñanza de la ciencia en general, y de la física y fisicoquímica en particular, hacen que estas disciplinas fundamentales sean vistas por los alumnos como algo abstracto y poco estimulante. El objetivo de la actividad propuesta en este proyecto es convertir el estudio de dichas materias en algo más interesante y participativo, motivando a los estudiantes mediante juegos basados en herramientas TIC y generando finalmente un mejor conocimiento gracias a la competición lúdica, al aprendizaje colaborativo y a la autoevaluación. En este sentido, nuestra propuesta se ha centrado en actividades interactivas basadas en la gamificación para el desarrollo de un aprendizaje proactivo de asignaturas complejas permitiendo al mismo tiempo una autoevaluación tanto a los estudiantes como a los profesores. De hecho, los alumnos, gracias a la resolución de preguntas en forma de juego han podido valorar su nivel de aprendizaje durante el desarrollo del curso y el profesor ha podido comprobar si sus clases son los suficientemente claras y/o cuales argumentos debería de profundizar y/o explicar de otra manera para obtener una mayor comprensión por parte de los estudiantes.
Enzyme Conformation Influences the Performance of Lipase‐powered Nanomotors
(2020) Wang, Lei; Marciello, Marzia; Estévez‐Gay, Miquel; Soto Rodríguez, Paul; Luengo Morato, Yurena; Iglesias‐Fernández, Javier; Huang, Xin; Osuna, Sílvia; Filice, Marco; Sánchez, Samuel
Enzyme-powered micro/nanomotors have myriads of potential applications in various areas. To efficiently reach those applications, it is necessary and critical to understand the fundamental aspects affecting the motion dynamics. Herein, we explored the impact of enzyme orientation on the performance of lipase-powered nanomotors by tuning the lipase immobilization strategies. The influence of the lipase orientation and lid conformation on substrate binding and catalysis was analyzed using molecular dynamics simulations. Besides, the motion performance indicates that the hydrophobic binding (via OTES) represents the best orienting strategy, providing 48.4 % and 95.4 % increase in diffusion coefficient compared to hydrophilic binding (via APTES) and Brownian motion (no fuel), respectively (with C[triacetin] of 100 mm). This work provides vital evidence for the importance of immobilization strategy and corresponding enzyme orientation for the catalytic activity and in turn, the motion performance of nanomotors, and is thus helpful to future applications.
Project number: 74
Las TICs: un instrumento de ayuda en las prácticas de laboratorio
(2022) Laurenti, Marco; Ovejero Paredes, Karina; Zabala Gutiérrez, Irene; Sanchez Sanche, Visitación; Yusta San Roman, Piedad; Contreras Cáceres, Rafael; Filice, Marco; López Cabarcos, Enrique; Marciello, Marzia; Méndez González, Diego; Rubio Retama, Benito Jorge; Villaverde Cantizano, Gonzalo
Desde la implantación del Espacio Europeo de Educación Superior nos encontramos ante dos grandes retos; el desarrollo metodológico y tecnológico en la formación y docencia on-line y en segundo lugar la cada vez más elevada especialización requerida a los estudiantes durante el Grado y Doble Grado en Farmacia. Esto hace que el foco de la formación de los estudiantes se desvíe de los conocimientos básicos y competencias de formación tanto en el trabajo experimental como en el conocimiento teórico. El proyecto se encuadra en el marco de la asignatura obligatoria Física Aplicada a Farmacia de Grado y Doble Grado en Farmacia, unas carreras con una elevada carga práctica y experimental.