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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Search Results

Now showing 1 - 10 of 252

Preventing bacterial adhesion on scaffolds for bone tissue engineering
(International Journal of Bioprinting, 2016) Sánchez Salcedo, Sandra; Colilla Nieto, Montserrat; Izquierdo Barba, Isabel; Vallet Regí, María Dulce Nombre
Bone implant infection constitutes a major sanitary concern which is associated to high morbidity and health costs. This manuscript focused on overviewing the main research efforts committed up to date to develop innovative alternatives to conventional treatments, such as those with antibiotics. These strategies mainly rely on chemical modifi-cations of the surface of biomaterials, such as providing it of zwitterionic nature, and tailoring the nanostructure surface of metal implants. These surface modifications have successfully allowed inhibition of bacterial adhesion, which is the first step to implant infection, and preventing long-term biofilm formation compared to pristine materials. These strate-gies could be easily applied to provide three-dimensional (3D) scaffolds based on bioceramics and metals, of which its manufacture using rapid prototyping techniques was reviewed. This opens the gates for the design and development of advanced 3D scaffolds for bone tissue engineering to prevent bone implant infections. Keywords: Antibacterial adhesion, biofilm formation, zwitterionic surfaces, nanostructured surfaces, rapid prototyping 3D scaffolds, bone tissue engineering.
From Proof-of-Concept Material to PEGylated and Modularly Targeted Ultrasound-Responsive Mesoporous Silica Nanoparticles
(Journal of Materials Chemistry B, 2018) Paris, J.L.; Villaverde, Gonzalo; Cabañas Criado, María Victoria; Manzano García, Miguel; Vallet Regí, María Dulce Nombre
In this work we present the synthesis, characterization and in vitro biological evaluation of PEGylated and actively-targeted ultrasound-responsive hybrid mesoporous silica nanoparticles. This work covers the development of the chemical strategies necessary to afford a modular nanocarrier starting from a proof-of-concept material presented in previous work. This functional ultrasound-responsive material can be adapted to different specific pathological conditions by carefully choosing the appropriate targeting moieties. The new ultrasound responsive material is able to target HeLa cells when conjugated with biotin or an RGD peptide. Ultrasound-responsive cytotoxicity towards cancer cells of doxorubicinloaded nanoparticles is demonstrated in an in vitro cytotoxicity assay.
Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non-viral Oligonucleotide Delivery Carriers
(Chemistry - A European Journal, 2015) Martínez, Angel; Fuentes Paniagua, Elena; Baeza, Alejandro; Sánchez Nieves, Javier; Cicuéndez Maroto, Mónica; Gómez, Rafael; Mata, F. Javier de la; González, Blanca; Vallet Regí, María Dulce Nombre
A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability.
Interaction between bovine serum albumin and mesoporous silica nanoparticles functionalized with biopolymers
(Chemical Engineering Journal, 2018) Nairi, Valentina; Medda, Sara; Piludu, Marco; Casula, Maria Francesca; Vallet Regí, María Dulce Nombre; Monduzzi, Maura; Salis, Andrea
Biomedical application of nanoparticles is largely associated to their fate in biological media which, in turn, is related to their surface properties. Surface functionalization plays a key role in determining biodegradation, cytotoxicity and biodistribution through interactions which may be mediated by the macromolecules occurring in biological media. A typical example is given by several proteins which lead to the formation of coated nanoparticles referred as protein corona. In this work we focus on mesoporous silica nanoparticles which, due to their intrinsic textural features, show potential as carriers for sustained drug release. Mesoporous silica nanoparticles functionalized by different biopolymers such as hyaluronic acid and chitosan were synthesized and characterized through small angle X-rays scattering, thermal analysis, and infrared spectroscopy. Biopolymer-coated mesoporous silica nanoparticles were used to investigate the interaction with bovine serum albumin, and to point out the role of different biopolymer coating. Gold-conjugated-bovine serum albumin was used to gain evidence on the occurrence of surface bound proteins enabling direct observation by transmission electron microscopy. Our findings provide insights on how different biopolymers affect the formation of a protein corona around functionalized mesoporous silica nanoparticles.
Decidua-derived mesenchymal stem cells as carriers of mesoporous silica nanoparticles. In vitro and in vivo evaluation on mammary tumors
(Acta Biomaterialia, 2016) Paris, Juan L.; Torre, Paz de la; Manzano, Miguel; Cabañas Criado, María Victoria; Flores, Ana I.; Vallet Regí, María Dulce Nombre
The potential use of human Decidua-derived mesenchymal stem cells (DMSCs) as a platform to carry mesoporous silica nanoparticles in cancer therapy has been investigated. Two types of nanoparticles were evaluated. The nanoparticles showed negligible toxicity to the cells, a fast uptake and a long retention inside them. Nanoparticle location in the cell was studied by colocalization with the lysosomes. Moreover, the in vitro and in vivo migration of DMSCs towards tumors was not modified by the evaluated nanoparticles. Finally, DMSCs transporting doxorubicin-loaded nanoparticles were capable of inducing cancer cell death in vitro.
Tuning dual-drug release from composite scaffolds for bone 2 regeneration
(International Journal of Pharmaceutics, 2015) Paris, J.L.; Román, M.; Cabañas Criado, María Victoria; Vallet Regí, María Dulce Nombre; Manzano García, Miguel
This work presents the tuning of drug-loaded scaffolds for bone regeneration as dual-drug delivery systems. Two therapeutic substances, zoledronic acid (anti-osteoporotic drug) and ibuprofen (antiinflammatory drug) were successfully incorporated in a controlled mannerinto three dimensional designed porous scaffolds of apatite/agarose composite. A high-performance liquid chromatography method was optimized to separate and simultaneously quantify the two drugs released from the dualdrug codelivery system. The multifunctional porous scaffolds fabricated show a very rapid delivery of anti-inflammatory (interesting to reduce inflammation after implantation), whereas the antiosteoporotic drug showed sustained release behaviour (important to promote bone regeneration). Since ibuprofen release was faster than desired, this drug was encapsulated in chitosan spheres which were then incorporated into the scaffolds, obtaining a release profile suitable for clinical application. The results obtained open the possibility to simultaneously incorporate two or more drugs to an osseous implant in a controlled way improving it for bone healing application.
Mesoporous silica nanoparticles grafted with a light-responsive protein shell for highly cytotoxic antitumoral therapy
(Journal of Materials Chemistry B, 2015) Martínez Carmona, Marina; Baeza, Alejandro; Rodriguez Milla, Miguel A.; García Castro, Javier; Vallet Regí, María Dulce Nombre
A novel phototriggered drug delivery nanocarrier, which exhibits very high tumor cytotoxicity against human tumoral cells, is presented. This device is based on mesoporous silica nanoparticles decorated with a biocompatible protein shell cleavable by light irradiation. The proteins that compose the protein shell (avidin, streptavidin and biotinylated transferrin) act as targeting and capping agents at the same time, avoiding the use of redundant systems. The light responsive behavior is provided by a biotinylated photocleavable cross-linker covalently grafted on the mesoporous surface, which suffers photocleavage by UV radiation (366 nm). Human tumoral cells incubated in the presence of a very low particle concentration enter into the apoptotic stage after a short irradiation time. Thus, the system described here could be applied to the treatment of exposed tumors that affect the skin, oesophagus, and stomach, among others, and are easily accessible for light irradiation.
Antimycobacterial effect of selenium nanoparticles on Mycobacterium tuberculosis.
(Frontiers Microbiology, 2020) Estévez Sánchez, Héctor; Palacios, Ainhoa; Gil, David; Anguita, Juan; Vallet Regí, María Dulce Nombre; González Ortiz, Blanca; Prados Rosales, Rafael; Luque-García, José L.
Tuberculosis remains the leading cause of death from a single infection agent worldwide. In recent years, the occurrence of tuberculosis cases caused by drug-resistant strains has spread, and is expected to continue to grow. Therefore, the development of new alternative treatments to the use of antibiotics is highly important. In that sense, nanotechnology can play a very relevant role, due to the unique characteristics of nanoparticles. In fact, different types of nanoparticles have already been evaluated both as potential bactericides and as efficient drug delivery vehicles. In this work, the use of selenium nanoparticles has been evaluated to inhibit the growth of two types of mycobacteria: Mycobacterium smegmatis and Mycobacterium tuberculosis. The results showed that selenium nanoparticles are able to inhibit the growth of both types of mycobacteria by damaging their cell envelope integrity. These results open a new opportunity for the use of this type of nanoparticles as antimycobacterial agents by themselves, or for the development of novel nanosystems that combine the action of these nanoparticles with other drugs.
Collagenase nanocapsules: An approach to fibrosis treatment
(Acta Biomaterialia, 2018) Vallet Regí, María Dulce Nombre; Ortiz Romero, Pablo Luis; Villegas Díaz, María Rocío; Baeza, Alejandro; Usategui Corral, Alicia; Pablos, José L.
Fibrosis is a common lesion in different pathologic diseases and defined by the excessive accumulation of collagen. Different approaches have been used to treat different conditions characterized by fibrosis. The FDA and EMA approved the use of collagenase to treat palmar fibromatosis (Dupuytren’s contracture). The EMA approved additionally its use in severe Peyronie’s disease, but it has been used off label in other conditions [1,2]. The approved treatment includes up to three (in palmar fibromatosis) or up to eight (in penile fibromatosis) injections followed by finger extension or penile modeling procedures, typically causing severe pain. Frequent single injections are adequate to treat palmar fibromatosis [3]. The need to repeatedly inject doses of this enzyme can be due to the labile nature of collagenase, which exhibits a complete activity loss after a short period of time. This study presents a novel strategy to manage this enzyme based on the synthesis of polymeric nanocapsules that contain collagenase encapsulated within their matrix. These nanocapsules have been engineered for achieving a gradual release of the encapsulated enzyme for a longer time, which can be up to ten days. The efficacy of these nanocapsules has been tested in a murine model of local dermal fibrosis, and the results demonstrate a reduction in fibrosis greater than that with the injection of free enzyme; this type of treatment showed a significant improvement compared to conventional therapy of free collagenase. Statement of Significance The use of proteins as therapeutic molecules has recently attracted great interest. Collagenase injection is the current treatment for fibrotic diseases. Unfortunately, proteins have a low stability and presume several repetition cycles to obtain an effective treatment. This article describes a novel treatment for these types of diseases using collagenase nanocapsules designed to exhibit a sustainable release of the encapsulated enzyme, which maintains the enzymatic activity for a long period of time. The therapeutic effect of nanocapsules was tested in a murine mouse model of local dermal fibrosis, and the results showed an important improved effect compared to the effect of the administration of free enzyme. These results indicate a high potential for this novel system to improve the current treatment for fibrotic diseases.
Effects of ipriflavone-loaded mesoporous nanospheres on the differentiation of endothelial cells and their modulation by macrophages.
(Nanomaterials, 2021) Casarrubios Molina, Laura; Polo Montalvo, Alberto; Serrano, María Concepción; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María Teresa
Angiogenic biomaterials for bone repair are being designed to promote vascularization and optimize tissue regeneration. The use of nanoparticles of bioactive materials loaded with different drugs represents an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. Ipriflavone (IP) prevents osteoporosis by inhibiting osteoclast activity and promoting preosteoblast differentiation into mature osteoblasts. Since endothelial progenitor cells (EPCs) are involved in the formation of blood vessels which are necessary for tissue regeneration, the isolation and characterization of porcine EPCs have been carried out in this work to evaluate the in vitro effects of unloaded (NanoMBGs) and IP-loaded nanospheres (NanoMBG-IPs) designed to stimulate osteogenesis. Because different signals between vascular and nonvascular cells are also essential to initiate angiogenic events, the potential modulating role of macrophages has been also evaluated by studying the expression of vascular endothelial growth factor receptor 2 (VEFGR2) as a specific marker for EPC differentiation under different culture conditions: a) EPCs in monoculture treated with NanoMBGs or NanoMBG-IPs, b) EPCs treated with conditioned media from basal, proinflammatory M1 and reparative M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, c) EPCs cocultured with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and d) EPCs cocultured with M2d angiogenic macrophages. Moreover, the endocytic mechanisms by which these nanospheres are incorporated by EPCs have been identified by using six endocytosis inhibitors (i.e. wortmannin, genistein, cytochalasin B, cytochalasin D, phenylarsine oxide and chlorpromazine) and before the addition of NanoMBGs labeled with fluorescein isothiocyanate. The results evidence the great potential of both NanoMBGs and NanoMBG-IPs to enhance VEFGR2 expression, directly related to angiogenesis, after intracellular incorporation by EPCs through different endocytic mechanisms including clathrin-dependent endocytosis, as the main entry mechanism, but also phagocytosis and caveolae-mediated uptake. The treatment of EPCs with culture media from basal, M1 and M2 macrophages and the development of cocultures of EPCs with macrophages in the absence and presence of these nanomaterials have also confirmed the maintenance of their angiogenic effect on EPCs even in the presence of phagocytic cells.