Person: Lozano Borregón, Daniel
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First Name
Daniel
Last Name
Lozano Borregón
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Inorgánica
Identifiers
19 results
Search Results
Now showing 1 - 10 of 19
Item Nanoparticles to Knockdown Osteoporosis-Related Gene and Promote Osteogenic Markers Expression for Osteoporosis Treatment(ACS Nano, 2019) Mora Raimundo, Patricia; Lozano Borregón, Daniel; Manzano García, Miguel; Vallet Regí, María Dulce NombreOsteoporosis is the most common disease involving bone degeneration. Current clinical treatments are not able to offer a satisfying curative effect, so the development of effective treatments is desired. Gene silencing through siRNA delivery has gained great attention as a potential treatment in bone diseases. SOST gene inhibits the Wnt signaling pathway reducing osteoblast differentiation. Consequently, silencing SOST gene with a specific siRNA could be a potential option to treat osteoporosis. Generally, siRNAs have very short half-life and poor transfection capacity, so an effective carrier is needed. In particular, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of nucleic acids. We took advantage of their high loading capacity to further load the pores with osteostatin, an osteogenic peptide. In this study we developed a system based on MSNs coated with poly(ethylenimine), which can effectively deliver SOST siRNA and osteostatin inside cells, with the consequent augmentation of osteogenic markers with a synergistic effect. This established the potential utility of MSNs to co-deliver both biomolecules to promote bone formation, being a potential alternative to treat osteoporosis.Item Non-replicative antibiotic resistance-free DNA vaccine encoding S and N proteins induces full protection in mice against SARS-CoV-2(Frontiers in Immunology, 2022) Alcolea Alcolea, Pedro José; Larraga, Jaime; Rodríguez-Martín, Daniel; Alonso, Ana; Loayza, Francisco; Rojas, José M.; Ruiz García, Silvia; Louloudes Lázaro, Andrés; Carlón, Ana B.; Sánchez Cordón, Pedro José; Nogales Altozano, Pablo; Redondo, Natalia; Manzano García, Miguel; Lozano Borregón, Daniel; Palomero, Jesús; Montoya, María; Vallet Regí, María Dulce Nombre; Martín García, Verónica; Sevilla, Noemí; Larraga, VicenteSARS-CoV-2 vaccines currently in use have contributed to controlling the COVID-19 pandemic. Notwithstanding, the high mutation rate, fundamentally in the spike glycoprotein (S), is causing the emergence of new variants. Solely utilizing this antigen is a drawback that may reduce the efficacy of these vaccines. Herein we pre ent a DNA vaccine candidate that contains the genes encoding the S and the nucleocapsid (N) proteins implemented into the nonreplicative mammalian expression plasmid vector, pPAL. This plasmid lacks antibiotic resistance genes and contains an alternative selectable marker for production. The S gene sequence was modified to avoid furin cleavage (Sfs). Potent humoral and cellular immune responses were observed in C57BL/6J mice vaccinated with pPAL-Sfs + pPAL-N following a prime/boost regimen by the intramuscular route applying in vivo electroporation. The immunogen fully protected K18-hACE2 mice against a lethal dose (105 PFU) of SARS-CoV-2. Viral replication was completely controlled in the lungs, brain, and heart of vaccinated mice. Therefore, pPAL-Sfs + pPAL-N is a promising DNA vaccine candidate for protection from COVID-19.Item Osteogenic Effect of ZnO-Mesoporous Glasses loaded with Osteostatin(Nanomaterials, 2018) Pérez, Rebeca; Sánchez-Salcedo, Sandra; Lozano Borregón, Daniel; Heras, Clara; Esbrit, Pedro; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their putative clinical use as scaffolds for bone regeneration. Their outstanding textural properties determine high bioactivity when compared with other bioactive materials. Moreover, their great pore volumes allow these glasses to be loaded with a wide range of biomolecules to stimulate new bone formation. In this study, an MBG with composition, in mol-%, 80%SiO2–15%CaO–5%P2O5 (Blank, BL) was compared with two analogous glasses containing 4% and 5% of ZnO (4ZN and 5ZN) before and after impregnation with osteostatin, a C-terminal peptide from parathyroid hormone-related protein (PTHrP107-111). Zn2+ ions were included in the glass for their bone growth stimulator properties, whereas osteostatin was added by its osteogenic properties. Glasses were characterized, and their cytocompatibility investigated in pre-osteoblastic MC3T3-E1 cell cultures. The simultaneous additions of osteostatin and Zn2+ ions provoked enhanced MC3T3-E1 cell viability and higher differentiation capacity, compared with either raw BL or MBGs supplemented only with osteostatin or Zn2+. These in vitro results show that osteostatin enhances the osteogenic effect of Zn2+-enriched glasses, suggesting the potential of this combined approach in bone tissue engineering applications.Item Engineering Mesoporous Silica Nanoparticles for Drug Delivery: where are we after two decades?(Chemical Society Reviews, 2022) Vallet Regí, María Dulce Nombre; Schüth, Ferdi; Lozano Borregón, Daniel; Colilla Nieto, Montserrat; Manzano García, MiguelThe present review details a chronological description of the events that took place during the development of mesoporous materials, their different synthetic routes and their use as drug delivery systems. The outstanding textural properties of these materials quickly inspired their translation to the nanoscale dimension leading to mesoporous silica nanoparticles (MSNs). The different aspects of introducing pharmaceutical agents into the pores of these nanocarriers, together with their possible biodistribution and clearance routes, would be here described. The development of smart nanocarriers able to release high local concentration of the therapeutic cargo on-demand after the application of certain stimuli would be here reviewed, together with the ability of delivering the therapeutic cargo to precise locations in the body. The huge progress in the design and development of MSNs for biomedical applications, including the potential treatment of different diseases, during the last 20 years will be here collected, together with the required work that still needs to be done to achieve the clinical translation of these materials. This review was conceived to stand out from past reports since aims to tell the story of the development of mesoporous materials and their use as drug delivery systems by some of the story makers, who could be considered to be among the pioneers in this area.Item Lectin-Conjugated pH-Responsive Mesoporous Silica Nanoparticles for Targeted Bone Cancer Treatment.(Acta Biomaterialia, 2017) Martínez Carmona, Marina; Lozano Borregón, Daniel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreA novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells. This multifunctional nanosystem exhibits a noticeable higher internalization degree into human osteosarcoma cells (HOS), overexpressing SA, compared to healthy preosteoblast cells (MC3T3-E1). Moreover, the results indicate that small DOX loading (2.5 µg mL−1) leads to almost 100% of osteosarcoma cell death in comparison with healthy bone cells, which significantly preserve their viability. Besides, this nanodevice has a cytotoxicity on tumor cells 8-fold higher than that caused by the free drug. These findings demonstrate that the synergistic combination of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards normal cells. This line of attack opens up new insights in targeted bone cancer therapy. Statement of Significance The development of highly selective and efficient tumor-targeted smart drug delivery nanodevices remains a great challenge in nanomedicine. This work reports the design and optimization of a multifunctional nanosystem based on mesoporous silica nanoparticles (MSNs) featuring selectivity towards human osteosarcoma cells and pH-responsive antitumor drug delivery capability. The novelty and originality of this manuscript relies on proving that the synergistic assembly of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards healthy cells, which constitutes a new paradigm in targeted bone cancer therapy.Item Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats(Journal of Biomedical Materials Research Part A, 2016) Ardura, Juan A.; Portal Núñez, Sergio; Lozano Borregón, Daniel; Gutiérrez Rojas, Irene; Sánchez Salcedo, Sandra; López Herradón, Ana; Mulero, Francisca; Villanueva Penacarrillo, Maria L.; Vallet Regí, María Dulce Nombre; Esbrit, PedroDiabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and -computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016.Item Engineered pH-Responsive Mesoporous Carbon Nanoparticles for Drug Delivery(ACS Applied Materials & Interfaces, 2020) Gisbert Garzarán, Miguel; Berkmann, Julia; Giasafaki, Dimitra; Lozano Borregón, Daniel; Spyrou, Konstantinos; Manzano García, Miguel; Steriotis, Theodore A; Duda, Georg; Schmidt-Bleek, Katharina; Charalambopoulou, Georgia; Vallet Regí, María Dulce NombreIn this work, two types of mesoporous carbon particles with different morphology, size and pore structure have been functionalized with a self-immolative polymer sensitive to changes in pH and tested as drug nanocarriers. It is shown that their textural properties allow significantly higher loading capacity compared to typical mesoporous silica nanoparticles. In vial release experiments of a model Ru dye at pH 7.4 and 5 confirm the pH-responsiveness of the hybrid systems, showing that only small amounts of the cargo are released at physiological pH, whereas at slightly acidic pH (e.g. that of lysosomes) self-immolation takes place and a significant amount of the cargo is released. Cytotoxicity studies using human osteosarcoma cells show that the hybrid nanocarriers are not cytotoxic by themselves but induce significant cell growth inhibition when loaded with a chemotherapeutic drug such as doxorubicin. In preparation of an in vivo application, in vial responsiveness of the hybrid system to short-term pH-triggering is confirmed. The consecutive in vivo study shows no substantial cargo release over a period of 96 hours under physiological pH conditions. Short-term exposure to acidic pH releases an experimental fluorescent cargo during and continuously after the triggering period over 72 hours.Item Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cell cultures(Acta Biomaterialia, 2019) Heras, Clara; Sánchez Salcedo, Sandra; Lozano Borregón, Daniel; Peña, Juan; Esbrit, Pablo; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2– 15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1-600 m) and big channels ( 1000 m), were prepared. These MBG scaffolds with or without osteostatin were evaluated in cell cultures of hMSCs. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications.Item Features of aminopropyl modified mesoporous silica nanoparticles. Implications on the active targeting capability(Materials Chemistry and Physics, 2018) Cabañas Criado, María Victoria; Lozano Borregón, Daniel; Torres-Pardo, A.; Sobrino, C.; González-Calvet, J.; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreAminopropyl 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.Item Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update(Expert Opinion on Drug Delivery, 2019) Castillo, Rafael R.; Lozano Borregón, Daniel; González, Blanca; Manzano García, Miguel; Izquierdo Barba, Isabel; Vallet Regí, María Dulce NombreIntroduction: Mesoporous silica nanoparticles (MSNs) are outstanding nanoplatforms for drug delivery. Herein, the most recent advances to turn MSN-based carriers into minimal side effect drug delivery agents are covered. Areas covered: This review summarizes the scientific advances dealing with MSNs for targeted and stimuli-responsive drug delivery since 2015. Delivery aspects to diseased tissues together with approaches to obtain smart MSNs able to respond to internal or external stimuli and their applications are here described. Special emphasis is done on the combination of two or more stimuli on the same nanoplatform and on combined drug therapy. Expert opinion: The use of MSNs in nanomedicine is a promising research field because they are outstanding platforms for treating different pathologies. This is possible thanks to their structural, chemical, physical and biological properties. However, there are certain issues that should be overcome to improve the suitability of MSNs for clinical applications. All materials must be properly characterized prior to their in vivo evaluation; furthermore, preclinical in vivo studies need to be standardized to demonstrate the MSNs clinical translation potential.