Person:
Vallet Regí, María Dulce Nombre

First Name

María Dulce Nombre

Last Name

Vallet Regí

URI

https://hdl.handle.net/20.500.14352/77741

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Inorgánica

Identifiers

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Now showing 1 - 9 of 9

Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem
(International Journal of Pharmaceutics, 2024) Aragoneses Cazorla, Guillermo; Álvarez-Fernández García, Roberto; Martínez López, Angelica; Gómez Gómez, María Milagros; Vallet Regí, María Dulce Nombre; Castillo Lluva, Sonia; González Ortiz, Blanca; Luque García, José Luis
This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a roundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.
Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits
(Acta Biomaterialia, 2024) García Lamas, Lorena; Lozano Borregón, Daniel; Jiménez Díaz, Verónica; Bravo Giménez, Beatriz; Sánchez Salcedo, Sandra; Abella, Mónica; Desco, Manuel; Jiménez Holguín, Javier; Vallet Regí, María Dulce Nombre; Cecilia López, David; Salinas Sánchez, Antonio Jesús
In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are ad- vanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2 –10CaO–5P2 O5 - x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rab- bits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the os- teostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteo- statin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice.
Magnetic colloidal nanoformulations to remotely trigger mechanotransduction for osteogenic differentiation
(Journal of Colloid And Interface Science, 2024) Gutiérrez Estévez, Manuel; Cicuéndez Maroto, Mónica; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre; González Ortiz, Blanca; Izquierdo Barba, Isabel
Nowadays, diseases associated with an ageing population, such as osteoporosis, require the development of new biomedical approaches to bone regeneration. In this regard, mechanotransduction has emerged as a discipline within the field of bone tissue engineering. Herein, we have tested the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs), obtained by the thermal decomposition method, with an average size of 13 nm, when exposed to the application of an external magnetic field for mechanotransduction in human bone marrowderived mesenchymal stem cells (hBM-MSCs). The SPIONs were functionalized with an Arg-Gly-Asp (RGD) peptide as ligand to target integrin receptors on cell membrane and used in colloidal state. Then, a comprehensive and comparative bioanalytical characterization of non-targeted versus targeted SPIONs was performed in terms of biocompatibility, cell uptake pathways and mechanotransduction effect, demonstrating the osteogenic
Tailoring the biological response of mesoporous bioactive materials
(Journal of Materials Chemistry B, 2013) Gómez Cerezo, María Natividad; Izquierdo Barba, Isabel; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre
Silica mesoporous nanomaterials have been proved to have meaningful application in biotechnology and biomedicine. Particularly, mesoporous bioactive glasses are recently gaining importance thanks to their bone regenerative properties. Moreover, the mesoporous nature of these materials makes them suitable for drug delivery applications, opening new lines in the field of bone therapies. In this work, we have developed innovative nanodevices based on the implementation of adenosine triphosphate (ATP) and ε-poly-l-lysine molecular gates using a mesoporous bioglass as an inorganic support. The systems have been previously proved to work properly with a fluorescence probe and subsequently with an antibiotic (levofloxacin) and an antitumoral drug (doxorubicin). The bioactivity of the prepared materials has also been tested, giving promising results. Finally, in vitro cell culture studies have been carried out; demonstrating that this gated devices can provide useful approaches for bone cancer and bone infection treatments.
Bioinspired extracellular vesicle-coated silica nanoparticles as selective delivery systems
(Materials Today Bio, 2023) Dumontel, Bianca; Jiménez-Jiménez, Carla; Vallet Regí, María Dulce Nombre; Manzano García, Miguel
In recent years, there has been a breakthrough in the integration of artificial nanoplatforms with natural biomaterials for the development of more efficient drug delivery systems. The formulation of bioinspired nanosystems, combining the benefits of synthetic nanoparticles with the natural features of biological materials, provides an efficient strategy to improve nanoparticle circulation time, biocompatibility and specificity toward targeted tissues. Among others biological materials, extracellular vesicles (EVs), membranous structures secreted by many types of cells composed by a protein rich lipid bilayer, have shown a great potential as drug delivery systems themselves and in combination with artificial nanoparticles. The reason for such interest relays on their natural properties, such as overcoming several biological barriers or migration towards specific tissues. Here, we propose the use of mesoporous silica nanoparticles (MSNs) as efficient and versatile nanocarriers in combination with tumor derived extracellular vesicles (EVs) for the development of selective drug delivery systems. The hybrid nanosystems demonstrated selective cellular internalization in parent cells, indicating that the EV targeting capabilities were efficiently transferred to MSNs by the developed coating strategy. As a result, EVs-coated MSNs provided an enhanced and selective intracellular accumulation of doxorubicin and a specific cytotoxic activity against targeted cancer cells, revealing these hybrid nanosystems as promising candidates for the development of targeted treatments.
Organically Modified Mesoporous Silica Nanoparticles against Bacterial Resistance
(Chemistry of Materials, 2023) Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre
Bacterial antimicrobial resistance is posed to become a major hazard to global health in the 21st century. An aggravating issue is the stalled antibiotic research pipeline, which requires the development of new therapeutic strategies to combat antibiotic-resistant infections. Nanotechnology has entered into this scenario bringing up the opportunity to use nanocarriers capable of transporting and delivering antimicrobials to the target site, overcoming bacterial resistant barriers. Among them, mesoporous silica nanoparticles (MSNs) are receiving growing attention due to their unique features, including large drug loading capacity, biocompatibility, tunable pore sizes and volumes, and functionalizable silanol-rich surface. This perspective article outlines the recent research advances in the design and development of organically modified MSNs to fight bacterial infections. First, a brief introduction to the different mechanisms of bacterial resistance is presented. Then, we review the recent scientific approaches to engineer multifunctional MSNs conceived as an assembly of inorganic and organic building blocks, against bacterial resistance. These elements include specific ligands to target planktonic bacteria, intracellular bacteria, or bacterial biofilm; stimuli-responsive entities to prevent antimicrobial cargo release before arriving at the target; imaging agents for diagnosis; additional constituents for synergistic combination antimicrobial therapies; and aims to improve the therapeutic outcomes. Finally, this manuscript addresses the current challenges and future perspectives on this hot research area.
Squaraine-loaded mesoporous silica nanoparticles for antimicrobial Photodynamic Therapy against bacterial infection
(Microporous and Mesoporous Materials, 2024) Melese Dereje, Degnet; García Fontecha, Ana; Pontremoli, Carlotta; González Ortiz, Blanca; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre; Izquierdo Barba, Isabel; Barbero, Nadia
Antimicrobial photodynamic therapy (aPDT) shows promise as a complementary or alternative approach to conventional antimicrobial treatments. Despite possessing some key advantages, many challenges remain, such as optimizing the delivery of photosensitizers, improving light penetration into tissues, and determining the most effective combinations of photosensitizers and light wavelengths for different infections. Moreover, addressing the challenges associated with the aggregation tendency and poor solubility of some photosensitizers, squaraine dyes (SQs) in particular, is crucial for unlocking their full potential in biomedical applications. This contribution focuses on designing innovative anophotosensitizers with antimicrobial properties using mesoporous silica nanoparticles (MSNs) loaded with a SQ dye (i.e. Br-SQ). MSNs before and after Br-SQ loading were deeply characterized using different techniques, proving the successful incorporation of the dye into the nanocarriers. Upon visible light (640 nm) irradiation, these nanosystems demonstrated remarkable antibacterial activities against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). Our results confirmed that MSNs are valuable nanocarriers of hydrophobic photosensitizers, such as Br-SQ, bringing up new opportunities to develop antibiotic-free anoformulations to treat bacterial infection while minimizing the risk of antimicrobial resistance.
Poly Lactic-co-Glycolic Acid (PLGA) Loaded with a Squaraine Dye as Photosensitizer for Antimicrobial Photodynamic Therapy
(Polymers, 2024) Melese Dereje, Degnet; Pontremoli, Carlotta; García Fontecha, Ana; Galliano, Simone; Colilla Nieto, Montserrat; González Ortiz, Blanca; Vallet Regí, María Dulce Nombre; Izquierdo Barba, Isabel; Barbero, Nadia
Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.
Osteoimmune Properties of Mesoporous Bioactive Nanospheres: A Study on T Helper Lymphocytes
(Nanomaterials, 2023) Casarrubios Molina, Laura; Cicuéndez Maroto, Mónica; Vallet Regí, María Dulce Nombre; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Feito Castellano, María José
Bioactive mesoporous glass nanospheres (nanoMBGs) charged with antiosteoporotic drugs have great potential for the treatment of osteoporosis and fracture prevention. In this scenario, cells of the immune system are essential both in the development of disease and in their potential to stimulate therapeutic effects. In the present work, we hypothesize that nanoMBGs loaded with ipriflavone can exert a positive osteoimmune effect. With this objective, we assessed the effects of non-loaded and ipriflavone-loaded nanoparticles (nanoMBGs and nanoMBG-IPs, respectively) on CD4+ Th2 lymphocytes because this kind of cell is implicated in the inhibition of osseous loss by reducing the RANKL/OPG relationship through the secretion of cytokines. The results indicate that nanoMBGs enter efficiently in CD4+ Th2 lymphocytes, mainly through phagocytosis and clathrindependent mechanisms, without affecting the function of these T cells or inducing inflammatory mediators or oxidative stress, thus maintaining the reparative Th2 phenotype. Furthermore, the incorporation of the anti-osteoporotic drug ipriflavone reduces the potential unwanted inflammatory response by decreasing the presence of ROS and stimulating intracellular anti-inflammatory cytokine release like IL-4. These results evidenced that nanoMBG loaded with ipriflavone exerts a positive osteoimmune effect.