Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights

Autores
López Estévez, Ana M.; Zhang, Y.; Medel, María; Arriaga, Iker; Sanjurjo, Lucía; Huck Iriart, Cristián; Abrescia, Nicola G. A.; Vicent, María J.; Ouyang, Defang; Torres, Dolores; Alonso, María José
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies (mAbs). Despite their increasing potential, mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular targets. Nanotechnology offers promising solutions to overcome this limitation, however, formulation challenges remain. These challenges are the limited loading capacity (often insufficient to achieve clinical dosing), the complex formulation methods, and the insufficient characterization of mAb-loaded nanocarriers. Here, we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies (HANAs) specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity (50%, w/w). HANAs composed by an mAb, modified HA and phosphatidylcholine (PC) resulted in sizes of ~ 100 nm and neutral surface charge. Computational modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and PC. HANAs composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy (cryo-TEM), asymmetrical flow field-flow fractionation (AF4), and small-angle X-ray scattering (SAXS). These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic HA. In vitro experiments in cancer cell lines and macrophages confirmed HANAs’ low toxicity and ability to transport mAbs to the intracellular space. The reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was assessed. In conclusion, these results underscore the suitability of HANAs technology to load and deliver biologicals, which holds promise for future clinical translation.
Fil: López Estévez, Ana M.. Universidad de Santiago de Compostela; España
Fil: Zhang, Y.. University Of Macau; China
Fil: Medel, María. Centro de Investigaciones Príncipe Felipe; España. Polymer Therapeutics Laboratory; España. CIBERONC Prince Felipe Research Centre; España
Fil: Arriaga, Iker. Basque Research and Technology Alliance; España
Fil: Sanjurjo, Lucía. Health Research Institute Of Santiago de Compostela; España
Fil: Huck Iriart, Cristián. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentina. ALBA Synchrotron Light Source; España
Fil: Abrescia, Nicola G. A.. IKERBASQUE; España. Basque Research and Technology Alliance; España
Fil: Vicent, María J.. Centro de Investigaciones Príncipe Felipe; España. Polymer Therapeutics Laboratory; España
Fil: Ouyang, Defang. University Of Macau; China
Fil: Torres, Dolores. Universidad de Santiago de Compostela; España
Fil: Alonso, María José. Universidad de Santiago de Compostela; España
Materia
Hyaluronic acid
Monoclonal antibody
Characterization
Delivery
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/268073
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/268073
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insightsLópez Estévez, Ana M.Zhang, Y.Medel, MaríaArriaga, IkerSanjurjo, LucíaHuck Iriart, CristiánAbrescia, Nicola G. A.Vicent, María J.Ouyang, DefangTorres, DoloresAlonso, María JoséHyaluronic acidMonoclonal antibodyCharacterizationDeliveryhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies (mAbs). Despite their increasing potential, mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular targets. Nanotechnology offers promising solutions to overcome this limitation, however, formulation challenges remain. These challenges are the limited loading capacity (often insufficient to achieve clinical dosing), the complex formulation methods, and the insufficient characterization of mAb-loaded nanocarriers. Here, we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies (HANAs) specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity (50%, w/w). HANAs composed by an mAb, modified HA and phosphatidylcholine (PC) resulted in sizes of ~ 100 nm and neutral surface charge. Computational modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and PC. HANAs composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy (cryo-TEM), asymmetrical flow field-flow fractionation (AF4), and small-angle X-ray scattering (SAXS). These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic HA. In vitro experiments in cancer cell lines and macrophages confirmed HANAs’ low toxicity and ability to transport mAbs to the intracellular space. The reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was assessed. In conclusion, these results underscore the suitability of HANAs technology to load and deliver biologicals, which holds promise for future clinical translation.Fil: López Estévez, Ana M.. Universidad de Santiago de Compostela; EspañaFil: Zhang, Y.. University Of Macau; ChinaFil: Medel, María. Centro de Investigaciones Príncipe Felipe; España. Polymer Therapeutics Laboratory; España. CIBERONC Prince Felipe Research Centre; EspañaFil: Arriaga, Iker. Basque Research and Technology Alliance; EspañaFil: Sanjurjo, Lucía. Health Research Institute Of Santiago de Compostela; EspañaFil: Huck Iriart, Cristián. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentina. ALBA Synchrotron Light Source; EspañaFil: Abrescia, Nicola G. A.. IKERBASQUE; España. Basque Research and Technology Alliance; EspañaFil: Vicent, María J.. Centro de Investigaciones Príncipe Felipe; España. Polymer Therapeutics Laboratory; EspañaFil: Ouyang, Defang. University Of Macau; ChinaFil: Torres, Dolores. Universidad de Santiago de Compostela; EspañaFil: Alonso, María José. Universidad de Santiago de Compostela; EspañaTsinghua Univ Press2024-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/268073López Estévez, Ana M.; Zhang, Y.; Medel, María; Arriaga, Iker; Sanjurjo, Lucía; et al.; Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights; Tsinghua Univ Press; Nano Research; 17; 10; 7-2024; 9111-91251998-0124CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/10.1007/s12274-024-6826-8info:eu-repo/semantics/altIdentifier/doi/10.1007/s12274-024-6826-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:27:20Zoai:ri.conicet.gov.ar:11336/268073instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:27:20.766CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
title Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
spellingShingle Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
López Estévez, Ana M.
Hyaluronic acid
Monoclonal antibody
Characterization
Delivery
title_short Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
title_full Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
title_fullStr Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
title_full_unstemmed Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
title_sort Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights
dc.creator.none.fl_str_mv López Estévez, Ana M.
Zhang, Y.
Medel, María
Arriaga, Iker
Sanjurjo, Lucía
Huck Iriart, Cristián
Abrescia, Nicola G. A.
Vicent, María J.
Ouyang, Defang
Torres, Dolores
Alonso, María José
author López Estévez, Ana M.
author_facet López Estévez, Ana M.
Zhang, Y.
Medel, María
Arriaga, Iker
Sanjurjo, Lucía
Huck Iriart, Cristián
Abrescia, Nicola G. A.
Vicent, María J.
Ouyang, Defang
Torres, Dolores
Alonso, María José
author_role author
author2 Zhang, Y.
Medel, María
Arriaga, Iker
Sanjurjo, Lucía
Huck Iriart, Cristián
Abrescia, Nicola G. A.
Vicent, María J.
Ouyang, Defang
Torres, Dolores
Alonso, María José
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hyaluronic acid
Monoclonal antibody
Characterization
Delivery
topic Hyaluronic acid
Monoclonal antibody
Characterization
Delivery
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies (mAbs). Despite their increasing potential, mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular targets. Nanotechnology offers promising solutions to overcome this limitation, however, formulation challenges remain. These challenges are the limited loading capacity (often insufficient to achieve clinical dosing), the complex formulation methods, and the insufficient characterization of mAb-loaded nanocarriers. Here, we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies (HANAs) specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity (50%, w/w). HANAs composed by an mAb, modified HA and phosphatidylcholine (PC) resulted in sizes of ~ 100 nm and neutral surface charge. Computational modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and PC. HANAs composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy (cryo-TEM), asymmetrical flow field-flow fractionation (AF4), and small-angle X-ray scattering (SAXS). These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic HA. In vitro experiments in cancer cell lines and macrophages confirmed HANAs’ low toxicity and ability to transport mAbs to the intracellular space. The reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was assessed. In conclusion, these results underscore the suitability of HANAs technology to load and deliver biologicals, which holds promise for future clinical translation.
Fil: López Estévez, Ana M.. Universidad de Santiago de Compostela; España
Fil: Zhang, Y.. University Of Macau; China
Fil: Medel, María. Centro de Investigaciones Príncipe Felipe; España. Polymer Therapeutics Laboratory; España. CIBERONC Prince Felipe Research Centre; España
Fil: Arriaga, Iker. Basque Research and Technology Alliance; España
Fil: Sanjurjo, Lucía. Health Research Institute Of Santiago de Compostela; España
Fil: Huck Iriart, Cristián. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentina. ALBA Synchrotron Light Source; España
Fil: Abrescia, Nicola G. A.. IKERBASQUE; España. Basque Research and Technology Alliance; España
Fil: Vicent, María J.. Centro de Investigaciones Príncipe Felipe; España. Polymer Therapeutics Laboratory; España
Fil: Ouyang, Defang. University Of Macau; China
Fil: Torres, Dolores. Universidad de Santiago de Compostela; España
Fil: Alonso, María José. Universidad de Santiago de Compostela; España
description The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies (mAbs). Despite their increasing potential, mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular targets. Nanotechnology offers promising solutions to overcome this limitation, however, formulation challenges remain. These challenges are the limited loading capacity (often insufficient to achieve clinical dosing), the complex formulation methods, and the insufficient characterization of mAb-loaded nanocarriers. Here, we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies (HANAs) specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity (50%, w/w). HANAs composed by an mAb, modified HA and phosphatidylcholine (PC) resulted in sizes of ~ 100 nm and neutral surface charge. Computational modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and PC. HANAs composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy (cryo-TEM), asymmetrical flow field-flow fractionation (AF4), and small-angle X-ray scattering (SAXS). These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic HA. In vitro experiments in cancer cell lines and macrophages confirmed HANAs’ low toxicity and ability to transport mAbs to the intracellular space. The reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was assessed. In conclusion, these results underscore the suitability of HANAs technology to load and deliver biologicals, which holds promise for future clinical translation.
publishDate 2024
dc.date.none.fl_str_mv 2024-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/268073
López Estévez, Ana M.; Zhang, Y.; Medel, María; Arriaga, Iker; Sanjurjo, Lucía; et al.; Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights; Tsinghua Univ Press; Nano Research; 17; 10; 7-2024; 9111-9125
1998-0124
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268073
identifier_str_mv López Estévez, Ana M.; Zhang, Y.; Medel, María; Arriaga, Iker; Sanjurjo, Lucía; et al.; Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights; Tsinghua Univ Press; Nano Research; 17; 10; 7-2024; 9111-9125
1998-0124
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/10.1007/s12274-024-6826-8
info:eu-repo/semantics/altIdentifier/doi/10.1007/s12274-024-6826-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Tsinghua Univ Press
publisher.none.fl_str_mv Tsinghua Univ Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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