pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies

Over the past few years, gene therapies have attracted much attention for the development of therapies for various conditions including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved t...

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Autores:
Ramírez Acosta, Carlos Manuel
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2019
Institución:
Universidad de los Andes
Repositorio:
Séneca: repositorio Uniandes
Idioma:
eng
OAI Identifier:
oai:repositorio.uniandes.edu.co:1992/45367
Acceso en línea:
http://hdl.handle.net/1992/45367
Palabra clave:
Química combinatoria
Nanopartículas
Nanotecnología
Química farmacéutica
Ingeniería
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
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dc.title.es_CO.fl_str_mv pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
title pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
spellingShingle pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
Química combinatoria
Nanopartículas
Nanotecnología
Química farmacéutica
Ingeniería
title_short pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
title_full pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
title_fullStr pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
title_full_unstemmed pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
title_sort pH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapies
dc.creator.fl_str_mv Ramírez Acosta, Carlos Manuel
dc.contributor.advisor.none.fl_str_mv Cruz Jiménez, Juan Carlos
Reyes Barrios, Luis Humberto
dc.contributor.author.none.fl_str_mv Ramírez Acosta, Carlos Manuel
dc.contributor.jury.none.fl_str_mv Ortiz Herrera, Pablo
dc.subject.armarc.es_CO.fl_str_mv Química combinatoria
Nanopartículas
Nanotecnología
Química farmacéutica
topic Química combinatoria
Nanopartículas
Nanotecnología
Química farmacéutica
Ingeniería
dc.subject.themes.none.fl_str_mv Ingeniería
description Over the past few years, gene therapies have attracted much attention for the development of therapies for various conditions including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved to reach clinical implementation eventually. Some of these challenges include low transfection rates, limited stability under physiological conditions, and low specificity towards the target cells. An avenue to overcome such issues is to deliver the therapies with the aid of potent cell-penetrating vectors, which include viral and non-viral vehicles. Non-viral vectors, such as nanostructured materials, have been successfully tested in drug and gene delivery. Here we propose the development of a nanostructured core-shell cell-penetrating vehicle composed of magnetite at the core, surrounded by a silver shell. A subsequent superficial conjugation of a pH-responsive polymer was used to assure that the vehicle can carry and release circular DNA. The obtained nanoconjugates were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope equipped with energy dispersive spectroscopy (SEM+EDS). Finally, a DNA load and delivery test were conducted to calculate the efficiency of the vehicle. The proposed nanoconjugate was capable of loading around 16% of the added DNA and released in a delivery stage. The study presented here provides a route for the development of gene delivery systems based on core-shell magnetic nanoparticles and pH-responsive polymers. Also, it highlights a methodology for the synthesis, functionalization, and loading of a circular DNA vector with the size typical of those for applications in CRISPR/Cas9 editing systems.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2020-09-03T15:57:30Z
dc.date.available.none.fl_str_mv 2020-09-03T15:57:30Z
dc.type.spa.fl_str_mv Trabajo de grado - Pregrado
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dc.format.extent.es_CO.fl_str_mv 12 hojas
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dc.publisher.es_CO.fl_str_mv Universidad de los Andes
dc.publisher.program.es_CO.fl_str_mv Ingeniería Química
dc.publisher.faculty.es_CO.fl_str_mv Facultad de Ingeniería
dc.publisher.department.es_CO.fl_str_mv Departamento de Ingeniería Química
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spelling Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Cruz Jiménez, Juan Carlosccd9a6dc-893a-4968-b2e3-ba11de54ffeb400Reyes Barrios, Luis Humbertovirtual::10464-1Ramírez Acosta, Carlos Manuelb927236d-0c30-4342-9df7-b7b7ea73b4f8400Ortiz Herrera, Pablo2020-09-03T15:57:30Z2020-09-03T15:57:30Z2019http://hdl.handle.net/1992/45367u827400.pdfinstname:Universidad de los Andesreponame:Repositorio Institucional Sénecarepourl:https://repositorio.uniandes.edu.co/Over the past few years, gene therapies have attracted much attention for the development of therapies for various conditions including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved to reach clinical implementation eventually. Some of these challenges include low transfection rates, limited stability under physiological conditions, and low specificity towards the target cells. An avenue to overcome such issues is to deliver the therapies with the aid of potent cell-penetrating vectors, which include viral and non-viral vehicles. Non-viral vectors, such as nanostructured materials, have been successfully tested in drug and gene delivery. Here we propose the development of a nanostructured core-shell cell-penetrating vehicle composed of magnetite at the core, surrounded by a silver shell. A subsequent superficial conjugation of a pH-responsive polymer was used to assure that the vehicle can carry and release circular DNA. The obtained nanoconjugates were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope equipped with energy dispersive spectroscopy (SEM+EDS). Finally, a DNA load and delivery test were conducted to calculate the efficiency of the vehicle. The proposed nanoconjugate was capable of loading around 16% of the added DNA and released in a delivery stage. The study presented here provides a route for the development of gene delivery systems based on core-shell magnetic nanoparticles and pH-responsive polymers. Also, it highlights a methodology for the synthesis, functionalization, and loading of a circular DNA vector with the size typical of those for applications in CRISPR/Cas9 editing systems."En los últimos años, las terapias genéticas han atraído mucha atención para el desarrollo de terapias para varias afecciones, como el cáncer, las enfermedades neurodegenerativas, las deficiencias de proteínas y los trastornos autoinmunes. A pesar de los beneficios de este enfoque, aún quedan por resolver varios desafíos para llegar a la implementación clínica. Algunos de estos desafíos incluyen tasas bajas de transfección, estabilidad limitada en condiciones fisiológicas y poca especificidad hacia las células diana. Una vía para superar tales problemas es administrar las terapias con la ayuda de potentes vectores de penetración celular, entre los cuales se evalúa el uso de sistemas de administración de fármacos. Los sistemas de administración de fármacos (DDS por sus siglas en inglés) tales como las nanopartículas basadas en lípidos o polímeros se pueden diseñar para mejorar las propiedades farmacológicas y terapéuticas de los fármacos administrados por vía parenteral. No obstante, uno de los principales problemas en los DDS es la prevención de una metabolización prematura o estabilización del transportador, es decir, permitir un tiempo de liberación apropiado para la terapia. Adicionalmente, los DDS tienen problemas de especificidad, por lo que se han realizado intentos para aumentar las acciones específicas de éstos, combinándolos con ligandos dirigidos contra antígenos o receptores de la superficie celular, un proceso llamado focalización mediada por ligando o activa. Para entender mejor los problemas de eficiencia y biodegradabilidad de los DDS es necesario dar un contexto del proceso que debe atravesar un transportador. Las moléculas terapéuticas (contenidas en el transportador) generalmente deben (I) cruzar una o varias membranas biológicas (mucosa, epitelio, endotelio), (II) deben difundirse a través de la membrana plasmática y (III) finalmente, tener acceso al organelo apropiado donde el objetivo biológico está ubicado."--Tomado del Formato de Documento de Grado.Ingeniero QuímicoPregrado12 hojasapplication/pdfengUniversidad de los AndesIngeniería QuímicaFacultad de IngenieríaDepartamento de Ingeniería Químicainstname:Universidad de los Andesreponame:Repositorio Institucional SénecapH-responsive, core-shell magnetite-silver nanoparticles for the guided transport and delivery of nucleotide cargoes : an avenue for highly-targeted gene therapiesTrabajo de grado - Pregradoinfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Texthttp://purl.org/redcol/resource_type/TPQuímica combinatoriaNanopartículasNanotecnologíaQuímica farmacéuticaIngenieríaPublicationhttps://scholar.google.es/citations?user=2vO8IrIAAAAJvirtual::10464-10000-0001-7251-5298virtual::10464-1https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001574664virtual::10464-17bc6dc94-4e9c-4245-8b42-9f7dbc69de83virtual::10464-17bc6dc94-4e9c-4245-8b42-9f7dbc69de83virtual::10464-1THUMBNAILu827400.pdf.jpgu827400.pdf.jpgIM Thumbnailimage/jpeg25561https://repositorio.uniandes.edu.co/bitstreams/655c1ec7-19b2-4398-9760-1db1fa74aad1/download3deca1072d30646d1dfa20ddbc555f55MD55ORIGINALu827400.pdfapplication/pdf574898https://repositorio.uniandes.edu.co/bitstreams/aeb3977e-8eec-4bbd-9f90-eeb65d054a0f/downloadd490c9f1aba332e236b36897477080aaMD51TEXTu827400.pdf.txtu827400.pdf.txtExtracted texttext/plain25721https://repositorio.uniandes.edu.co/bitstreams/e2f65812-40c6-4f28-b18c-ae02865b8572/download0c305269cd2279fe9c5a33add2727717MD541992/45367oai:repositorio.uniandes.edu.co:1992/453672024-03-13 14:11:32.026http://creativecommons.org/licenses/by-nc-nd/4.0/restrictedhttps://repositorio.uniandes.edu.coRepositorio institucional Sénecaadminrepositorio@uniandes.edu.co