Person: Lozano Borregón, Daniel
Universidad Complutense de Madrid
Faculty / Institute
Química en Ciencias Farmacéuticas
Now showing 1 - 10 of 28
- PublicationAnalysis of Islet-1, Nkx2.1, Pax6, and Orthopedia in the forebrain of the sturgeon Acipenser ruthenus identifies conserved prosomeric characteristics(Wiley, 2021-09-21) López, Jesús M.; Jiménez, Sara; Morona Arribas, Ruth; Lozano Borregón, Daniel; Moreno García, NereaThe distribution patterns of a set of conserved brain developmental regulatory transcription factors were analyzed in the forebrain of the basal actinopterygian fish Acipenser ruthenus, consistent with the prosomeric model. In the telencephalon, the pallium was characterized by ventricular expression of Pax6. In the subpallium, the combined expression of Nkx2.1/Islet-1 (Isl1) allowed to propose ventral and dorsal areas, as the septo-pallidal (Nkx2.1/Isl1+) and striatal derivatives (Isl1+), respectively, and a dorsal portion of the striatal derivatives, ventricularly rich in Pax6 and devoid of Isl1 expression. Dispersed Orthopedia (Otp) cells were found in the supracommissural and posterior nuclei of the ventral telencephalon, related to the medial portion of the amygdaloid complex. The preoptic area was identified by the Nkx2.1/Isl1 expression. In the alar hypothalamus, an Otp-expressing territory, lacking Nkx2.1/Isl1, was identified as the paraventricular domain. The adjacent subparaventricular domain (Spa) was subdivided in a rostral territory expressing Nkx2.1 and an Isl1+ caudal one. In the basal hypothalamus, the tuberal region was defined by the Nkx2.1/Isl1 expression and a rostral Otp-expressing domain was identified. Moreover, the Otp/Nkx2.1 combination showed an additional zone lacking Isl1, tentatively identified as the mamillary area. In the diencephalon, both Pax6 and Isl1 defined the prethalamic domain, and within the basal prosomere 3, scattered Pax6- and Isl1-expressing cells were observed in the posterior tubercle. Finally, a small group of Pax6 cells was observed in the pretectal area. These results improve the understanding of the forebrain evolution and demonstrate that its basic bauplan is present very early in the vertebrate lineage.
- PublicationAntibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus(Elsevier, 2022-10-28) Aguilera Correa, John Jairo; Gisbert Garzarán, Miguel; Mediero, A.; Pablo Velasco, David de; Fernández Aceñero, María Jesús; Lozano Borregón, Daniel; Esteban, J.; Vallet Regí, MaríaOsteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis. Statement of significance In this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect.
- PublicationNanoparticles for the potential treatment of osteoporosis.(Future Medicine, 2020-10-14) Lozano Borregón, Daniel; Vallet Regí, María; Manzano García, Miguel; Mora Raimundo, PatriciaIn this original editorial piece, María Vallet-Regí, Patricia Mora-Raimundo, Daniel Lozano and Miguel Manzano (all at the Universidad Complutense de Madrid, Spain) discuss the use of nanoparticles for the potential treatment of osteoporosis, in light of some of their recently published work in the field.
- PublicationMesoporous Silica Nanoparticles for Targeting Subcellular Organelles.(MDPI, 2020-12-18) Gisbert Garzarán, Miguel; Lozano Borregón, Daniel; Vallet Regí, MaríaCurrent chemotherapy treatments lack of great selectivity towards tumoral cells, which 13 leads to nonspecific drug distribution and subsequent side effects. In this regard, the use of 14 nanoparticles able to encapsulate and release therapeutic agents has attracted growing attention. In 15 this sense, mesoporous silica nanoparticles (MSNs) have been widely employed as drug carriers 16 owing to their exquisite physico-chemical properties. Because MSNs present a surface full of silanol 17 groups, they can be easily functionalized to endow the nanoparticles with many different 18 functionalities, including the introduction of moieties with affinity for the cell membrane or relevant 19 compartments within the cell, thus increasing the efficacy of the treatments. This review manuscript 20 will provide the state-of-the-art on MSNs functionalized for targeting subcellular compartments, 21 focusing on the cytoplasm, the mitochondria and the nucleus.
- PublicationNanoantibiotics Based in Mesoporous Silica Nanoparticles: New Formulations for Bacterial Infection Treatment.(MDPI, 2021-11-29) Álvarez Corchado, Elena; González Ortiz, Blanca; Lozano Borregón, Daniel; Doadrio Villarejo, Antonio Luis; Colilla, Montserrat; Izquierdo Barba, IsabelThis review focuses on the design of mesoporous silica nanoparticles for infection treat‐ment. Written within a general context of contributions in the field, this manuscript highlights the major scientific achievements accomplished by Prof. Vallet‐Regí’s research group in the field of silica‐based mesoporous materials for drug delivery. The aim is to bring out her pivotal role on the envisage of a new era of nanoantibiotics by using a deep knowledge on mesoporous materials as drug delivery systems and applying cutting‐edge technologies to design and engineer advanced nanoweapons to fight infection. This review has been divided in two main sections: the first part overviews the influence of the textural and chemical properties of silica‐based mesoporous materials on the loading and release of antibiotic molecules, depending on the host‐guest interactions.Furthermore, this section also remarks the potential of molecular modelling in the design and comprehension of the performance of these release systems. The second part describes the more recent advances in the use of mesoporous silica nanoparticles as versatile nanoplatforms for the development of novel targeted and stimuli‐responsive antimicrobial nanoformulations for future application in personalized infection therapies.
- PublicationZnO-mesoporous glass scaffolds loaded with osteostatin and mesenchymal cells improve bone healing in a rabbit bone defect.(Springer, 2020-08-25) Lozano Borregón, Daniel; Gil Alvaroba, J; Heras Rubio, Clara; Sánchez Salcedo, Sandra; Gómez Palacio, V. E.; Gómez Blasco, A; Doadrio Villarejo, Juan Carlos; Vallet Regí, María; Salinas Sánchez, Antonio J.The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2–10.3CaO–3.3P2O5–4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN+MSC, 4ZN+OST or 4ZN+MSC+OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice.
- PublicationFeatures of aminopropyl modified mesoporous silica nanoparticles. Implications on the active targeting capability(Elsevier, 2018-12-01) Cabañas Criado, Victoria; Lozano Borregón, Daniel; Torres-Pardo, A.; Sobrino, C.; González-Calvet, J.; Arcos Navarrete, Daniel; Vallet Regí, MaríaAminopropyl modified mesoporous SiO2 nanoparticles, MCM-41 type, have been synthesized by the co-condensation method from tetraethylorthosilicate (TEOS) and aminopropyltriethoxysilane (APTES). By means of modifying TEOS/APTES ratio we have carried out an in-depth characterization of the nanoparticles as a function of APTES content. Surface charge and nanoparticles morphology were strongly influenced by the amount of APTES and particles changed from hexagonal to bean-like morphology insofar APTES increased. Besides, the porous structure was also affected, showing a contraction of the lattice parameter and pore size, while increasing the wall thickness. These results bring about new insights about the nanoparticles formation during the co-condensation process. The model proposed herein considers that different interactions stablished between TEOS and APTES with the structure directing agent have consequences on pore size, wall thickness and particle morphology. Finally, APTES is an excellent linker to covalently attach active targeting agents such as folate groups. We have hypothesized that APTES could also play a role in the biological behavior of the nanoparticles. So, the internalization efficiency of the nanoparticles has been tested with cancerous LNCaP and non-cancerous preosteoblast-like MC3T3-E1 cells. The results indicate a cooperative effect between aminopropylsilane presence and folic acid, only for the cancerous LNCaP cell line.
- PublicationParathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin-glutaraldehyde biopolymer-coated hydroxyapatite(Elsevier, 2014-07) Lozano Borregón, Daniel; Sánchez Salcedo, Sandra; Portal Núñez, Sergio; Vila, Mercedes; López Herradón, Ana; Ardura, Juan A.; Mulero, Francisca; Gómez Barrena, Enrique; Vallet Regí, María; Esbrit, PedroBiopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HA(GIu)) scaffolds would produce an optimal biomaterial for tissue engineering applications. HA(GIu) scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HA(Giu) implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule I, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HA(Giu) scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HA(GIu) scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
- PublicationIn Vitro and In Vivo Response of Zinc-Containing Mesoporous Bioactive Glasses in a Sheep Animal Model(MDPI, 2022-11-11) Jiménez Holguín, Javier; Arcos Navarrete, Daniel; Lozano Borregón, Daniel; Sainz-Pardo Sanz, Melchor; Ortega Medina, Luis; Enciso, S; Fernández Tomé, Blanca; López Güemes, Idoia; Sánchez Margallo, Francisco Miguel; Casarrubios Molina, Laura; Portolés Pérez, María Teresa; Vallet Regí, MaríaZinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models.In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn2+ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly highe r values of viability and expression of early markers of celldifferentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn2+ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue.
- PublicationOsteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles(Wiley-VCH GmbH, 2021-06-06) Mora Raimundo, Patricia; Lozano Borregón, Daniel; Benito de las Heras, Manuel; Mulero, Francisca; Manzano García, Miguel; Vallet Regí, MaríaNanotechnology changed the concept of treatment for a variety of diseases, producing a huge impact regarding drug and gene delivery. Among the different targeted diseases, osteoporosis has devastating clinical and economic consequences. Since current osteoporosis treatments present several side effects, new treatment approaches are needed. Recently, the application of small interfering RNA (siRNA) has become a promising alternative. Wnt/β-catenin signaling pathway controls bone development and formation. This pathway is negatively regulated by sclerostin, which knock-down through siRNA application would potentially promote bone formation. However, the major bottleneck for siRNA-based treatments is the necessity of a delivery vector, bringing nanotechnology as a potential solution. Among the available nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of siRNAs. The mesoporous structure of MSNs permits the delivery of siRNAs together with another biomolecule, achieving a combination therapy. Here, we evaluate the effectiveness of a new potential osteoporosis treatment based on MSNs. Our proposed system was effective in delivering SOST siRNA and osteostatin through systemic injection to bone tissue. The nanoparticle administration produced an increase expression of osteogenic related genes improving the bone microarchitecture. The treated osteoporotic mice recovered values of a healthy situation approaching to osteoporosis remission.