Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells

Autores
Calienni, Maria Natalia; Sandoval Acuña, Cristian; Potomová, Petra; Ybarra, David Emanuel; Truksa, Jaroslav; Martinetti Montanari, Jorge Anibal
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: Vismodegib (VDG), a Smoothened inhibitor approved for basal cell carcinoma, has potential for repurposing in other tumors in which Hedgehog (Hh) signaling contributes to malignancy. However, systemic VDG treatment is associated with relevant adverse effects, and its effective delivery to cutaneous targets remains challenging, supporting the exploration of drug delivery systems for its administration.Methods: Here, we first screened the response to VDG across four murine tumor cell lines-B16 melanoma, 4T1 mammary carcinoma, Colon-26 colon carcinoma, and LLC1 Lewis lung carcinoma-and then evaluated whether nanocarrier-based delivery could modify its activity in melanoma cells.Results: Free VDG produced moderate effects across the screened models, with B16 emerging as the most responsive model showing evidence of growth inhibition together with modulation of Hh-related markers. In this setting, encapsulation of VDG into ultradeformable liposomes (UDL), specially designed for topical application, significantly changed the biological response to treatment, producing a stronger cytotoxic response, concentration-dependent inhibition of cell population expansion, and increased accumulation of dead cells compared with the free drug. An exploratory PAMAM G4.5 dendrimer-based formulation did not show detectable biological effects at the tested concentration, which was constrained by the need to maintain subtoxic dendrimer levels. Although no significant transcriptional changes were detected at the analyzed time point, reduced Gli-1 expression at higher concentrations suggested some degree of Hh pathway modulation by UDL-VDG. However, the enhanced biological effect of UDL-VDG could not be explained solely by canonical Hh inhibition, and responses varied across melanoma models.Discussion: Overall, these results show that ultradeformable liposomal delivery potentiates the in vitro anti-melanoma activity of VDG and supports its further exploration as a repurposing strategy for candidate non-metastatic cutaneous melanoma. More broadly, these findings support the rationale for topical nanocarrier-based delivery as an approach that could potentially improve local drug availability while helping to reduce some of the limitations associated with systemic administration.
Fil: Calienni, Maria Natalia. Universidad Nacional de Hurlingham; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sandoval Acuña, Cristian. Universidad de La Frontera; Chile
Fil: Potomová, Petra. Czech Academy Of Sciences.; República Checa
Fil: Ybarra, David Emanuel. Universidad Nacional de Hurlingham; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Truksa, Jaroslav. Czech Academy Of Sciences.; República Checa
Fil: Martinetti Montanari, Jorge Anibal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Hurlingham; Argentina
Materia
Vismodegib
Hedgehog signaling
Drug repurposing
melanoma
ultradeformable liposomes
dendrimers
nano-based drug delivery
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/290363
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/290363
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cellsCalienni, Maria NataliaSandoval Acuña, CristianPotomová, PetraYbarra, David EmanuelTruksa, JaroslavMartinetti Montanari, Jorge AnibalVismodegibHedgehog signalingDrug repurposingmelanomaultradeformable liposomesdendrimersnano-based drug deliveryhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Introduction: Vismodegib (VDG), a Smoothened inhibitor approved for basal cell carcinoma, has potential for repurposing in other tumors in which Hedgehog (Hh) signaling contributes to malignancy. However, systemic VDG treatment is associated with relevant adverse effects, and its effective delivery to cutaneous targets remains challenging, supporting the exploration of drug delivery systems for its administration.Methods: Here, we first screened the response to VDG across four murine tumor cell lines-B16 melanoma, 4T1 mammary carcinoma, Colon-26 colon carcinoma, and LLC1 Lewis lung carcinoma-and then evaluated whether nanocarrier-based delivery could modify its activity in melanoma cells.Results: Free VDG produced moderate effects across the screened models, with B16 emerging as the most responsive model showing evidence of growth inhibition together with modulation of Hh-related markers. In this setting, encapsulation of VDG into ultradeformable liposomes (UDL), specially designed for topical application, significantly changed the biological response to treatment, producing a stronger cytotoxic response, concentration-dependent inhibition of cell population expansion, and increased accumulation of dead cells compared with the free drug. An exploratory PAMAM G4.5 dendrimer-based formulation did not show detectable biological effects at the tested concentration, which was constrained by the need to maintain subtoxic dendrimer levels. Although no significant transcriptional changes were detected at the analyzed time point, reduced Gli-1 expression at higher concentrations suggested some degree of Hh pathway modulation by UDL-VDG. However, the enhanced biological effect of UDL-VDG could not be explained solely by canonical Hh inhibition, and responses varied across melanoma models.Discussion: Overall, these results show that ultradeformable liposomal delivery potentiates the in vitro anti-melanoma activity of VDG and supports its further exploration as a repurposing strategy for candidate non-metastatic cutaneous melanoma. More broadly, these findings support the rationale for topical nanocarrier-based delivery as an approach that could potentially improve local drug availability while helping to reduce some of the limitations associated with systemic administration.Fil: Calienni, Maria Natalia. Universidad Nacional de Hurlingham; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sandoval Acuña, Cristian. Universidad de La Frontera; ChileFil: Potomová, Petra. Czech Academy Of Sciences.; República ChecaFil: Ybarra, David Emanuel. Universidad Nacional de Hurlingham; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Truksa, Jaroslav. Czech Academy Of Sciences.; República ChecaFil: Martinetti Montanari, Jorge Anibal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Hurlingham; ArgentinaFrontiers Media2026-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/290363Calienni, Maria Natalia; Sandoval Acuña, Cristian; Potomová, Petra; Ybarra, David Emanuel; Truksa, Jaroslav; et al.; Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells; Frontiers Media; Frontiers in Medical Technology; 8; 6-2026; 1-132673-3129CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmedt.2026.1826970/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmedt.2026.1826970info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:59:22Zoai:ri.conicet.gov.ar:11336/290363instacron: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:34982026-08-25 14:59:22.684CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
title Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
spellingShingle Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
Calienni, Maria Natalia
Vismodegib
Hedgehog signaling
Drug repurposing
melanoma
ultradeformable liposomes
dendrimers
nano-based drug delivery
title_short Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
title_full Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
title_fullStr Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
title_full_unstemmed Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
title_sort Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells
dc.creator.none.fl_str_mv Calienni, Maria Natalia
Sandoval Acuña, Cristian
Potomová, Petra
Ybarra, David Emanuel
Truksa, Jaroslav
Martinetti Montanari, Jorge Anibal
author Calienni, Maria Natalia
author_facet Calienni, Maria Natalia
Sandoval Acuña, Cristian
Potomová, Petra
Ybarra, David Emanuel
Truksa, Jaroslav
Martinetti Montanari, Jorge Anibal
author_role author
author2 Sandoval Acuña, Cristian
Potomová, Petra
Ybarra, David Emanuel
Truksa, Jaroslav
Martinetti Montanari, Jorge Anibal
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Vismodegib
Hedgehog signaling
Drug repurposing
melanoma
ultradeformable liposomes
dendrimers
nano-based drug delivery
topic Vismodegib
Hedgehog signaling
Drug repurposing
melanoma
ultradeformable liposomes
dendrimers
nano-based drug delivery
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Introduction: Vismodegib (VDG), a Smoothened inhibitor approved for basal cell carcinoma, has potential for repurposing in other tumors in which Hedgehog (Hh) signaling contributes to malignancy. However, systemic VDG treatment is associated with relevant adverse effects, and its effective delivery to cutaneous targets remains challenging, supporting the exploration of drug delivery systems for its administration.Methods: Here, we first screened the response to VDG across four murine tumor cell lines-B16 melanoma, 4T1 mammary carcinoma, Colon-26 colon carcinoma, and LLC1 Lewis lung carcinoma-and then evaluated whether nanocarrier-based delivery could modify its activity in melanoma cells.Results: Free VDG produced moderate effects across the screened models, with B16 emerging as the most responsive model showing evidence of growth inhibition together with modulation of Hh-related markers. In this setting, encapsulation of VDG into ultradeformable liposomes (UDL), specially designed for topical application, significantly changed the biological response to treatment, producing a stronger cytotoxic response, concentration-dependent inhibition of cell population expansion, and increased accumulation of dead cells compared with the free drug. An exploratory PAMAM G4.5 dendrimer-based formulation did not show detectable biological effects at the tested concentration, which was constrained by the need to maintain subtoxic dendrimer levels. Although no significant transcriptional changes were detected at the analyzed time point, reduced Gli-1 expression at higher concentrations suggested some degree of Hh pathway modulation by UDL-VDG. However, the enhanced biological effect of UDL-VDG could not be explained solely by canonical Hh inhibition, and responses varied across melanoma models.Discussion: Overall, these results show that ultradeformable liposomal delivery potentiates the in vitro anti-melanoma activity of VDG and supports its further exploration as a repurposing strategy for candidate non-metastatic cutaneous melanoma. More broadly, these findings support the rationale for topical nanocarrier-based delivery as an approach that could potentially improve local drug availability while helping to reduce some of the limitations associated with systemic administration.
Fil: Calienni, Maria Natalia. Universidad Nacional de Hurlingham; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sandoval Acuña, Cristian. Universidad de La Frontera; Chile
Fil: Potomová, Petra. Czech Academy Of Sciences.; República Checa
Fil: Ybarra, David Emanuel. Universidad Nacional de Hurlingham; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Truksa, Jaroslav. Czech Academy Of Sciences.; República Checa
Fil: Martinetti Montanari, Jorge Anibal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Hurlingham; Argentina
description Introduction: Vismodegib (VDG), a Smoothened inhibitor approved for basal cell carcinoma, has potential for repurposing in other tumors in which Hedgehog (Hh) signaling contributes to malignancy. However, systemic VDG treatment is associated with relevant adverse effects, and its effective delivery to cutaneous targets remains challenging, supporting the exploration of drug delivery systems for its administration.Methods: Here, we first screened the response to VDG across four murine tumor cell lines-B16 melanoma, 4T1 mammary carcinoma, Colon-26 colon carcinoma, and LLC1 Lewis lung carcinoma-and then evaluated whether nanocarrier-based delivery could modify its activity in melanoma cells.Results: Free VDG produced moderate effects across the screened models, with B16 emerging as the most responsive model showing evidence of growth inhibition together with modulation of Hh-related markers. In this setting, encapsulation of VDG into ultradeformable liposomes (UDL), specially designed for topical application, significantly changed the biological response to treatment, producing a stronger cytotoxic response, concentration-dependent inhibition of cell population expansion, and increased accumulation of dead cells compared with the free drug. An exploratory PAMAM G4.5 dendrimer-based formulation did not show detectable biological effects at the tested concentration, which was constrained by the need to maintain subtoxic dendrimer levels. Although no significant transcriptional changes were detected at the analyzed time point, reduced Gli-1 expression at higher concentrations suggested some degree of Hh pathway modulation by UDL-VDG. However, the enhanced biological effect of UDL-VDG could not be explained solely by canonical Hh inhibition, and responses varied across melanoma models.Discussion: Overall, these results show that ultradeformable liposomal delivery potentiates the in vitro anti-melanoma activity of VDG and supports its further exploration as a repurposing strategy for candidate non-metastatic cutaneous melanoma. More broadly, these findings support the rationale for topical nanocarrier-based delivery as an approach that could potentially improve local drug availability while helping to reduce some of the limitations associated with systemic administration.
publishDate 2026
dc.date.none.fl_str_mv 2026-06
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/11336/290363
Calienni, Maria Natalia; Sandoval Acuña, Cristian; Potomová, Petra; Ybarra, David Emanuel; Truksa, Jaroslav; et al.; Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells; Frontiers Media; Frontiers in Medical Technology; 8; 6-2026; 1-13
2673-3129
CONICET Digital
CONICET
url http://hdl.handle.net/11336/290363
identifier_str_mv Calienni, Maria Natalia; Sandoval Acuña, Cristian; Potomová, Petra; Ybarra, David Emanuel; Truksa, Jaroslav; et al.; Ultradeformable liposomal delivery of vismodegib modulates its biological activity in melanoma cells; Frontiers Media; Frontiers in Medical Technology; 8; 6-2026; 1-13
2673-3129
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://www.frontiersin.org/articles/10.3389/fmedt.2026.1826970/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fmedt.2026.1826970
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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 13.24418

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