Nanobioconjugados con base en nanopartículas de sílice y/o fullerenol, Buforina II y la proteína OmpA, con potencial uso como vehículos de penetración celular

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dc.contributor.advisorCruz Jiménez, Juan Carlos
dc.contributor.advisorDuarte Ruiz, Alvaro
dc.contributor.authorRavelo Nieto, Eduardo
dc.contributor.educationalvalidatorJavier Cifuentes
dc.contributor.financerUniversidad de los Andes
dc.contributor.researchgroupNuevos Materiales Nano y Supramolecularesspa
dc.contributor.researchgroupDepartamento de Ingeniería Biomédica - Universidad de los Andesspa
dc.date.accessioned2022-08-24T14:35:33Z
dc.date.available2022-08-24T14:35:33Z
dc.date.issued2022-05-05
dc.descriptionilustraciones, fotografías, graficasspa
dc.description.abstractDiferentes barreras biológicas son generalmente responsables de la limitada liberación de cargos a nivel celular, como estrategia terapéutica. Previamente, se desarrolló una nueva familia de nanobioconjugados con capacidad de penetración celular y de escape a la ruta endosomal, inmovilizando el péptido Buforina II (BUF-II) y la proteína OmpA en nanopartículas (NPs) de magnetita. Aquí, proponemos ampliar este enfoque a nanopartículas de sílice (SNPs) y fullerenol (F) como soportes nanoestructurados para la conjugación de estos potentes agentes de penetración celular, ya que la misma molécula conjugada a diferentes nanotransportadores puede exhibir diferentes interacciones con compartimentos subcelulares. Los nanobioconjugados obtenidos (OmpA-SNPs, BUF-II-PEG12-SNPs, OmpA-F y BUF-II-PEG12-F) se caracterizaron mediante técnicas como espectroscopia infrarroja (FT-IR), UV-vis, Dispersión Dinámica de Luz (DLS), Movilidad Electroforética, Microscopía Electrónica de Barrido (SEM), Microscopía Electrónica de Transmisión (TEM), Análisis termogravimétrico (TGA), Difracción de Rayos X (DRX), y Microscopía confocal para evaluar composición, tamaño, carga, morfología, y confirmar la conjugación de dichos agentes translocantes. Los nanobioconjugados mostraron alta capacidad de internalización en células Vero (ATCC® CCL-81) y THP-1 (ATCC® TIB-202), sin afectar la viabilidad celular, no mostraron efecto hemolítico significativo, así como baja tendencia a inducir agregación plaquetaria. Adicionalmente, mostraron diferente comportamiento en el tráfico intracelular y escape endosomal en estas dos líneas celulares, lo que una vez más demostró el potencial de estos materiales para abordar los desafíos de liberación citoplasmática de fármacos o el desarrollo de terapias para el tratamiento de enfermedades de depósito lisosomal. (Texto tomado de la fuente)spa
dc.description.abstractSeveral biological barriers are generally responsible for the limited delivery of cargoes at the cellular level, as a therapeutic strategy. Previously, a new family of nanobioconjugates capable of cell penetration and endosomal escape was developed by immobilizing the Buforin II (BUF-II) peptide and the OmpA protein on magnetite nanoparticles (NPs). Here, we propose to extend this approach to silica NPs (SNPs) and fullerenol (F) as nanostructured supports for the conjugation of these potent cell-penetrating agents, as the same molecule conjugated to different nanocarriers may exhibit different interactions with subcellular compartments. The obtained nanobioconjugates(OmpA-SNPs, BUF-II-PEG12-SNPs, OmpA-F, and BUF-II-PEG12-F) were characterized via Fourier transform infrared spectroscopy (FT-IR), UV-vis, Dynamic Light Scattering (DLS), Electrophoretic Mobility, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric analysis (TGA), X-ray diffraction (XRD) techniques, and confocal microscopy was conducted to evaluate size, charge, composition, morphology, and to confirm the conjugation of these translocating agents on the NPs. Nanobioconjugates showed high internalization capacity in Vero cells (ATCC® CCL-81) and THP-1 cells (ATCC® TIB-202), without affecting cell viability, showed no significant hemolytic effect, as well as low propensity to induce platelet aggregation. Additionally, nanobioconjugates showed different intracellular trafficking and endosomal escape behavior in these two cell lines, showing once again the potential of these materials to address the challenges of cytoplasmic drugs delivery or the development of therapeutics for the treatment of lysosomal storage diseases.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMaestría en Ciencias-Químicaspa
dc.description.researchareaBionanotecnología y Biomaterialesspa
dc.format.extent101 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/82059
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Químicaspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Químicaspa
dc.relation.indexedRedColspa
dc.relation.indexedLaReferenciaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/spa
dc.subject.ddc570 - Biología::572 - Bioquímicaspa
dc.subject.proposalNanobioconjugadospa
dc.subject.proposalBuforina IIspa
dc.subject.proposalProteína OmpAspa
dc.subject.proposalNanopartículas de sílicespa
dc.subject.proposalFullerenolspa
dc.subject.proposalInternalización celularspa
dc.subject.proposalEscape endosomalspa
dc.subject.proposalnanobioconjugateseng
dc.subject.proposalSilica nanoparticleseng
dc.subject.proposalCellular uptakeeng
dc.subject.proposalEndosomal escapeeng
dc.titleNanobioconjugados con base en nanopartículas de sílice y/o fullerenol, Buforina II y la proteína OmpA, con potencial uso como vehículos de penetración celularspa
dc.title.translatedNanobioconjugates based on silica nanoparticles and/or fullerenol, Buforin II and the OmpA protein, with potential use as cell penetration vehicleseng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa
oaire.fundernameUniversidad Nacional de Colombiaspa
oaire.fundernameUniversidad de los Andesspa
oaire.fundernameMinciencias grant 689-2018spa

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