Person: Gómez Graña, Sergio
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First Name
Sergio
Last Name
Gómez Graña
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
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5 results
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Item Reversible nanogate system for Mesoporous Silica Nanoparticles based on Diels-Alder adducts.(Chemistry - A European Journal, 2018) Castillo Romero, Rafael; Hernández-Escobar, David; Gómez Graña, Sergio; Vallet Regí, María Dulce NombreThe implementation of nanoparticles as nanomedicines require from sophisticated surface modifications in order to reduce immune response and enhance recognition abilities. In addition to that, Mesoporous Silica nanoparticles present extraordinary host-guest abilities and facile surface functionalization. These two factors make them ideal candidates for the development of novel drug delivery systems, at the expense of increasing the structural complexity. With this idea in mind, a system of triggerable and tunable silica nanoparticles was developed for its application as drug delivery nanocarriers. For that purpose, Diels-Alder cycloaddition adducts were chosen as thermalresponsive units; that permitted to bind Au nanocaps able to block the pores and allow the incorporation of targeting fragments. The capping efficiency was tested under different thermal conditions, obtaining outstanding efficiencies within the physiological range and mild temperatures, as well as enhanced releases under pulsing heating cycles which showed the best release profiles.Item Supramolecular Control over the Interparticle Distance in Gold Nanoparticle Arrays by Cyclodextrin Polyrotaxanes(Nanomaterials, 2018) Coelho, Joao Paulo; Osío Barcina, José de Jesús; Junquera González, Elena; Aicart Sospedra, Emilio; Tardajos Rodríguez, Gloria; Gómez Graña, Sergio; Cruz Gil, Pablo; Salgado, Cástor; Díaz Núñez, Pablo; Peña Rodríguez, Ovidio; Guerrero Martínez, AndrésAmphiphilic nonionic ligands, synthesized with a fixed hydrophobic moiety formed by a thiolated alkyl chain and an aromatic ring, and with a hydrophilic tail composed of a variable number of oxyethylene units, were used to functionalize spherical gold nanoparticles (AuNPs) in water. Steady-state and time-resolved fluorescence measurements of the AuNPs in the presence of α-cyclodextrin (α-CD) revealed the formation of supramolecular complexes between the ligand and macrocycle at the surface of the nanocrystals. The addition of α-CD induced the formation of inclusion complexes with a high apparent binding constant that decreased with the increasing oxyethylene chain length. The formation of polyrotaxanes at the surface of AuNPs, in which many α-CDs are trapped as hosts on the long and linear ligands, was demonstrated by the formation of large and homogeneous arrays of self-assembled AuNPs with hexagonal close packing, where the interparticle distance increased with the length of the oxyethylene chain. The estimated number of α-CDs per polyrotaxane suggests a high rigidization of the ligand upon complexation, allowing for nearly perfect control of the interparticle distance in the arrays. This degree of supramolecular control was extended to arrays formed by AuNPs stabilized with polyethylene glycol and even to binary arrays. Electromagnetic simulations showed that the enhancement and distribution of the electric field can be finely controlled in these plasmonic arrays.Item Targeted Chemo‐Photothermal Therapy: A Nanomedicine Approximation to Selective Melanoma Treatment(2018) Villaverde Cantizano, Gonzalo; Gómez Graña, Sergio; Guisasola, Eduardo ; García García, María Isabel; Hanske, Christoph ; Liz‐Marzán, Luis M. ; Baeza, Alejandro ; Vallet Regí, María Dulce NombreMelanoma is one of the most severe public health issues worldwide, not only because of the high number of cases but also for its poor prognosis in late stages. Therefore, early diagnosis and efficient treatment are key toward a future solution. However, melanoma is highly resistant to cytotoxicity in its metastatic form. In this context, a therapeutic strategy based on a targeted chemo-photothermal nanotransporter for cytotoxic compounds is proposed. This approach comprises the use of core–multishell gold nanorods, coated with mesoporous silica and further covered with a thermosensitive polymer, which is vectorized for selective internalization in melanoma cells. The proposed nanoformulation is capable of releasing the transported cytotoxic compounds on demand, in response to near-IR irradiation, with high selectivity and efficacy against malignant cells, even at low concentrations, thereby providing a new tool against melanoma disease.Item Mesoporous silica nanoparticles containing silver as novel antimycobacterial agents against Mycobacterium tuberculosis(Colloids and Surfaces B: Biointerfaces, 2020) Montalvo Quirós, Sandra; Gómez Graña, Sergio; Vallet Regí, María Dulce Nombre; Prados Rosales, Rafael; González Ortiz, Blanca; Luque García, José LuisTuberculosis remains today a major public health issue with a total of 9 million new cases and 2 million deaths annually. The lack of an effective vaccine and the increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics, anticipate a complicated scenario in the near future. The use of nanoparticles features as an alternative to antibiotics in tackling this problem due to their potential effectiveness in resistant bacterial strains. In this context, silver nanoparticles have demonstrated high bactericidal efficacy,although their use is limited by their relatively high toxicity, which calls for the design of nanocarriers that allow silver based nanoparticles to be safely delivered to the target cells or tissues. In this work mesoporous silica nanoparticles are used as carriers of silver based nanoparticles as antimycobacterial agent against Mtb. Two different synthetic approaches have been used to afford, on the one hand, a 2D hexagonal mesoporous silica nanosystem which contains silver bromide nanoparticles distributed all through the silica network and, on the other hand, a core@shell nanosystem with metallic silver nanoparticles as core and mesoporous silica shell in a radial mesoporous rearrangement. Both materials have demonstrated good antimycobacterial capacity in in vitro test using Mtb, being lower the minimum inhibitory concentration for the nanosystem which contains silver bromide. Therefore, the interaction of this material with the mycobacterial cell has been studied by cryo-electron microscopy, establishing a direct connection between the antimycobactericidal effect observed and the damage induced in the cell envelope.Item Nanoparticles for multimodal antivascular therapeutics: Dual drug release, photothermal and photodynamic therapy(2020) Paris, Juan L.; Villaverde Cantizano, Gonzalo; Gómez Graña, Sergio; Vallet Regí, María Dulce NombreThe poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endotheliumtargeted nanoparticle (employing an RGD-containing peptide) capable of co-delivering two anti-vascular drugs (one anti-angiogenic drug and one vascular disruption agent) is here presented. Furthermore, the nanodevice presents two additional anti-vascular capabilities upon activation by Near-Infrared light: provoking local hyperthermia (by gold nanorods in the system) and generating toxic reactive oxygen species (by the presence of a photosensitizer). RGD-targeting is shown to increase uptake by HUVEC cells, and while the nanoparticles are shown not to be toxic for these cells, upon Near-Infrared irradiation their almost complete killing is achieved. The combination of all four therapeutic modalities is then evaluated in an ex ovo fibrosarcoma xenograft model, which shows a significant reduction in the number of blood vessels irrigating the xenografts when the nanoparticles are present, as well as the destruction of the existing blood vessels upon irradiation. These results suggest that the combination of different antivascular therapeutic strategies in a single nanocarrier appears promising and should be further explored in the future.