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
7 results
Search Results
Now showing 1 - 7 of 7
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 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 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 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.Item Self-Immolative Polymers as novel pH-responsive gate keepers for drug delivery(RSC Advances, 2016) Gisbert Garzarán, Miguel; Lozano Borregón, Daniel; Vallet Regí, María Dulce Nombre; Manzano García, MiguelA novel pH-sensitive nanocarrier based on mesoporous silica nanoparticles with self-immolative polymers blocking the pore openings is presented. Triggered release by acid pH is demonstrated, together with their in vitro biocompatibility and effective cell internalisation, which makes this new material a promising candidate for future applications in cancer treatment.Item Pleiotrophin-Loaded Mesoporous Silica Nanoparticles as a Possible Treatment for Osteoporosis(Pharmaceutics, 2023) Lozano Borregón, Daniel; Leiva, Beatriz; Gómez-Escalonilla, Inés; Portal Núñez, Sergio; Gortázar, Arancha R.; Manzano García, Miguel; Vallet Regí, María Dulce NombreOsteoporosis is the most common type of bone disease. Conventional treatments are based on the use of antiresorptive drugs and/or anabolic agents. However, these treatments have certain limitations, such as a lack of bioavailability or toxicity in non-specific tissues. In this regard, pleiotrophin (PTN) is a protein with potent mitogenic, angiogenic, and chemotactic activity, with implications in tissue repair. On the other hand, mesoporous silica nanoparticles (MSNs) have proven to be an effective inorganic drug-delivery system for biomedical applications. In addition, the surface anchoring of cationic polymers, such as polyethylenimine (PEI), allows for greater cell internalization, increasing treatment efficacy. In order to load and release the PTN to improve its effectiveness, MSNs were successfully internalized in MC3T3-E1 mouse pre-osteoblastic cells and human mesenchymal stem cells. PTN-loaded MSNs significantly increased the viability, mineralization, and gene expression of alkaline phosphatase and Runx2 in comparison with the PTN alone in both cell lines, evidencing its positive effect on osteogenesis and osteoblast differentiation. This proof of concept demonstrates that MSN can take up and release PTN, developing a potent osteogenic and differentiating action in vitro in the absence of an osteogenic differentiation-promoting medium, presenting itself as a possible treatment to improve bone-regeneration and osteoporosis scenarios.