Sistema de Salut de Catalunya
Institut Català de la Salut
[Gustà MF] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. [Edel MJ] Hospital Clínic de Barcelona, Servei Immunologia-IDIBAPS, Barcelona, Spain. Unit of Anatomy and Embryology, Universitat Autònoma de Barcelona, Faculty of Medicine, Barcelona, Spain. University of Western Australia, Faculty of Medicine, Discipline of Medical Sciences and Genetics, School of Biomedical Sciences, Perth, WA, Australia. [Salazar VA] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Alvarez-Palomo B] Banc de Sang i Teixits, Cell Therapy Service, Barcelona, Spain. [Juan M] Hospital Clínic de Barcelona, Servei Immunologia-IDIBAPS, Barcelona, Spain. [Broggini M] IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. [Puntes V] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-06-06T07:44:38Z
2023-06-06T07:44:38Z
2023-05-09
Gene therapeutics; Gold nanoparticles; Safety
Terapia génica; Nanopartículas de oro; Seguridad
Teràpia gènica; Nanopartícules d'or; Seguretat
Introduction: Gene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic ‘non-viral’ vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery. Methods: We herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell. Results and Discussion: Tested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides.
We acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER,UE) proyectos de I+D+i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019-103436) cofunded by the European Union and Generalitat de Catalunya (2017-SGR-1431). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya.
Article
Published version
English
Endocitosi; Nanopartícules; Transfecció; RNA; PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Endocytosis; TECHNOLOGY, INDUSTRY, AND AGRICULTURE::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles; CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Gene Transfer Techniques::Transfection; FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::endocitosis; TECNOLOGÍA, INDUSTRIA Y AGRICULTURA::tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas; COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::ARN mensajero; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::técnicas de transferencia génica::transfección
Frontiers Media
Frontiers in Immunology;14
https://doi.org/10.3389/fimmu.2023.1128582
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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