Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics
MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nuclea...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/264232 |
| Acceso en línea: | http://hdl.handle.net/10261/264232 https://api.elsevier.com/content/abstract/scopus_id/85119046061 |
| Access Level: | acceso abierto |
| Palabra clave: | Cancer therapy miRNAs delivery Nanocarriers Nanovesicles |
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Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| title |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| spellingShingle |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics Boloix, Ariadna Cancer therapy miRNAs delivery Nanocarriers Nanovesicles |
| title_short |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| title_full |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| title_fullStr |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| title_full_unstemmed |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| title_sort |
Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics |
| dc.creator.none.fl_str_mv |
Boloix, Ariadna Feiner-Gracia, Natalia Köber, Mariana Repetto, Javier Pascarella, Rosa Soriano, Aroa Masanas, Marc Segovia, Nathaly Vargas Nadal, Guillem Merlo Mas, Josep Danino, Dganit Abutbul-Ionita, Inbal Foradada, Laia Roma, Josep Córdoba, Alba Sala Vergés, Santiago Toledo, Josep Sánchez de Gallego, Soledad Veciana, Jaume Albertazzi, Lorenzo Segura, Miguel F. Ventosa, Nora |
| author |
Boloix, Ariadna |
| author_facet |
Boloix, Ariadna Feiner-Gracia, Natalia Köber, Mariana Repetto, Javier Pascarella, Rosa Soriano, Aroa Masanas, Marc Segovia, Nathaly Vargas Nadal, Guillem Merlo Mas, Josep Danino, Dganit Abutbul-Ionita, Inbal Foradada, Laia Roma, Josep Córdoba, Alba Sala Vergés, Santiago Toledo, Josep Sánchez de Gallego, Soledad Veciana, Jaume Albertazzi, Lorenzo Segura, Miguel F. Ventosa, Nora |
| author_role |
author |
| author2 |
Feiner-Gracia, Natalia Köber, Mariana Repetto, Javier Pascarella, Rosa Soriano, Aroa Masanas, Marc Segovia, Nathaly Vargas Nadal, Guillem Merlo Mas, Josep Danino, Dganit Abutbul-Ionita, Inbal Foradada, Laia Roma, Josep Córdoba, Alba Sala Vergés, Santiago Toledo, Josep Sánchez de Gallego, Soledad Veciana, Jaume Albertazzi, Lorenzo Segura, Miguel F. Ventosa, Nora |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Educación, Cultura y Deporte (España) Ministerio de Economía y Competitividad (España) Ministerio de Ciencia, Innovación y Universidades (España) Instituto de Salud Carlos III Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (España) Matem lo Bitxo Asociación Española Contra el Cáncer Generalitat de Catalunya Boloix, Ariadna [0000-0002-1648-5589] Köber, Mariana [0000-0001-9962-7900] Soriano, Aroa [0000-0001-9659-1471] Masanas, Marc [0000-0002-2249-8554] Segovia, Nathaly [0000-0001-8814-6095] Vargas Nadal, Guillem [0000-0003-4383-1325] Merlo Mas, Josep [0000-0002-3698-6655] Danino, Dganit [0000-0002-9782-4940] Foradada, Laia [0000-0002-0589-4360] Roma, Josep [0000-0001-7692-6123] Toledo, Josep Sánchez de [0000-0002-1034-1920] Gallego, Soledad [0000-0002-4712-9624] Veciana, Jaume [0000-0003-1023-9923] Albertazzi, Lorenzo [0000-0002-6837-0812] Segura, Miguel F. [0000-0003-0916-3618] Ventosa, Nora [0000-0002-8008-4974] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Cancer therapy miRNAs delivery Nanocarriers Nanovesicles |
| topic |
Cancer therapy miRNAs delivery Nanocarriers Nanovesicles |
| description |
MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/264232 https://api.elsevier.com/content/abstract/scopus_id/85119046061 |
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http://hdl.handle.net/10261/264232 https://api.elsevier.com/content/abstract/scopus_id/85119046061 |
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Inglés |
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Inglés |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Wiley-VCH |
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Wiley-VCH |
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Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA TherapeuticsBoloix, AriadnaFeiner-Gracia, NataliaKöber, MarianaRepetto, JavierPascarella, RosaSoriano, AroaMasanas, MarcSegovia, NathalyVargas Nadal, GuillemMerlo Mas, JosepDanino, DganitAbutbul-Ionita, InbalForadada, LaiaRoma, JosepCórdoba, AlbaSala Vergés, SantiagoToledo, Josep Sánchez deGallego, SoledadVeciana, JaumeAlbertazzi, LorenzoSegura, Miguel F.Ventosa, NoraCancer therapymiRNAs deliveryNanocarriersNanovesiclesMicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (<150 nm) and composition. These nanovesicles are colloidal stable (>24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics.The funding was received by Ministerio de Educación, Cultura y Deporte (Grant no. FPU16/01099), Ministerio de Economía, Industria y Competividad (Grants MAT2016-80820-R, MAT2016-80826-R and SAF2016-75241-R), the Ministry of Science and Innovation (MINECO) of Spain through grant PID2019-105622RB-I00, from Instituto de Salud Carlos III (Grant no. CP16/00006, PI17/00564, PI20/00530, DTS20/00018) (Co-funded by European Regional Development Fund/European Social Fund) “Investing in your future”), from the EuroNanoMed II platform through the NanoVax project, from CIBER-BBN through grant TAG-SMARTLY, Joan Petit Foundation, Asociación Matem Lo Bitxo and Asociación Española Contra el Cáncer (Grant no. LABAE18009SEGU), as well as, Generalitat de Catalunya through the Centres de Recerca de Catalunya (CERCA) programme and grant no. 2017-SGR-918, and from Agency for Management of University and Research Grants (AGAUR) (Grant no 2018LLAV0064 and SIFECAT IU68-010017). Furthermore, ICMAB-CSIC acknowledges support from the MINECO through the Severo Ochoa Programme for Centres of Excellence in R&D (SEV-2015-0496 and CEX2019-000917-S). Quatsome production and their physicochemical characterization was performed by the ICTS “NANBIOSIS,” more specifically in the Biomaterial Processing and Nanostructuring Unit (U6), Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBER-BBN) located at the Institute of Materials Science of Barcelona (ICMAB-CSIC). The authors thank the UAB Microscopy service for their help in recording cryo-TEM images. The authors also thank Mr. Adolfo de Hoyos-Limon for pKa measurements, Ms. Patricia Pérez for her help in in vitro experiments, the members of Laboratory Animal Service Unit of Vall d'Hebron Research Institute for their help in the in vivo experiment. The authors thank Editage (www.editage.com) and Ms. Christine O'Hara for English language correction. The authors acknowledge Biorender.com for allowing the adaptation of their templates. Retrieved from https://app.biorender.com/biorender-templates.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewedWiley-VCHMinisterio de Educación, Cultura y Deporte (España)Ministerio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIICentro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (España)Matem lo BitxoAsociación Española Contra el CáncerGeneralitat de CatalunyaBoloix, Ariadna [0000-0002-1648-5589]Köber, Mariana [0000-0001-9962-7900]Soriano, Aroa [0000-0001-9659-1471]Masanas, Marc [0000-0002-2249-8554]Segovia, Nathaly [0000-0001-8814-6095]Vargas Nadal, Guillem [0000-0003-4383-1325]Merlo Mas, Josep [0000-0002-3698-6655]Danino, Dganit [0000-0002-9782-4940]Foradada, Laia [0000-0002-0589-4360]Roma, Josep [0000-0001-7692-6123]Toledo, Josep Sánchez de [0000-0002-1034-1920]Gallego, Soledad [0000-0002-4712-9624]Veciana, Jaume [0000-0003-1023-9923]Albertazzi, Lorenzo [0000-0002-6837-0812]Segura, Miguel F. [0000-0003-0916-3618]Ventosa, Nora [0000-0002-8008-4974]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/264232https://api.elsevier.com/content/abstract/scopus_id/85119046061reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MAT2016-80820-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MAT2016-80826-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75241-info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105622RB-I00info:eu-repo/grantAgreement/MICIU/Plan Estatal de investigación Científica y Técnica y de Innovación 2017-2020/CEX2019-000917-SSmall (Weinheim an der Bergstrasse, Germany)http://dx.doi.org/10.1002/smll.202101959Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2642322026-05-22T06:33:51Z |
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