Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis

[Background]: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also m...

Full description

Bibliographic Details
Authors: Palencia-Campos, Adrián, Ruiz-Cañas, Laura, Abal-Sanisidro, Marcelina, López-Gil, Juan Carlos, Batres-Ramos, Sandra, Mendes Saraiva, Sofía, Yagüe, Balbino, Navarro, Diego, Alcalá, Sonia, Rubiolo, Juan A., Bidan, Nadège, Sánchez, Laura, Mura, Simona, Hermann, Patrick C., Fuente, María de la, Sainz, Bruno Jr.
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/383804
Online Access:http://hdl.handle.net/10261/383804
Access Level:Open access
Keyword:Pancreatic ductal adenocarcinoma
Tumor-associated macrophages
Tumor microenvironment
Lipid nanoemulsions
Galunisertib
Liver metastasis
Reprogramming
id ES_3947983bce7feeaeb155199d07e2b0d4
oai_identifier_str oai:digital.csic.es:10261/383804
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
spellingShingle Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
Palencia-Campos, Adrián
Pancreatic ductal adenocarcinoma
Tumor-associated macrophages
Tumor microenvironment
Lipid nanoemulsions
Galunisertib
Liver metastasis
Reprogramming
title_short Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_full Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_fullStr Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_full_unstemmed Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_sort Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
dc.creator.none.fl_str_mv Palencia-Campos, Adrián
Ruiz-Cañas, Laura
Abal-Sanisidro, Marcelina
López-Gil, Juan Carlos
Batres-Ramos, Sandra
Mendes Saraiva, Sofía
Yagüe, Balbino
Navarro, Diego
Alcalá, Sonia
Rubiolo, Juan A.
Bidan, Nadège
Sánchez, Laura
Mura, Simona
Hermann, Patrick C.
Fuente, María de la
Sainz, Bruno Jr.
author Palencia-Campos, Adrián
author_facet Palencia-Campos, Adrián
Ruiz-Cañas, Laura
Abal-Sanisidro, Marcelina
López-Gil, Juan Carlos
Batres-Ramos, Sandra
Mendes Saraiva, Sofía
Yagüe, Balbino
Navarro, Diego
Alcalá, Sonia
Rubiolo, Juan A.
Bidan, Nadège
Sánchez, Laura
Mura, Simona
Hermann, Patrick C.
Fuente, María de la
Sainz, Bruno Jr.
author_role author
author2 Ruiz-Cañas, Laura
Abal-Sanisidro, Marcelina
López-Gil, Juan Carlos
Batres-Ramos, Sandra
Mendes Saraiva, Sofía
Yagüe, Balbino
Navarro, Diego
Alcalá, Sonia
Rubiolo, Juan A.
Bidan, Nadège
Sánchez, Laura
Mura, Simona
Hermann, Patrick C.
Fuente, María de la
Sainz, Bruno Jr.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Conferencia de Rectores de las Universidades Españolas
Consejo Superior de Investigaciones Científicas (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Instituto de Salud Carlos III
European Commission
Fundación Científica Asociación Española Contra el Cáncer
German Cancer Aid
Axencia Galega de Innovación
Fundación la Caixa
EMBO
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Pancreatic ductal adenocarcinoma
Tumor-associated macrophages
Tumor microenvironment
Lipid nanoemulsions
Galunisertib
Liver metastasis
Reprogramming
topic Pancreatic ductal adenocarcinoma
Tumor-associated macrophages
Tumor microenvironment
Lipid nanoemulsions
Galunisertib
Liver metastasis
Reprogramming
description [Background]: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
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
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/383804
url http://hdl.handle.net/10261/383804
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCI2019-103725
https://doi.org/10.1186/s12951-024-03010-5
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406154853974016
spelling Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasisPalencia-Campos, AdriánRuiz-Cañas, LauraAbal-Sanisidro, MarcelinaLópez-Gil, Juan CarlosBatres-Ramos, SandraMendes Saraiva, SofíaYagüe, BalbinoNavarro, DiegoAlcalá, SoniaRubiolo, Juan A.Bidan, NadègeSánchez, LauraMura, SimonaHermann, Patrick C.Fuente, María de laSainz, Bruno Jr.Pancreatic ductal adenocarcinomaTumor-associated macrophagesTumor microenvironmentLipid nanoemulsionsGalunisertibLiver metastasisReprogramming[Background]: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.[Results]: In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem’s therapeutic effect in the context of human PDAC metastasis.[Conclusions]: The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was supported by the MICIU Joint Transnational Call for Proposals/PCI 2019–1 (PCI2019-103725; B.S.,Jr.) and the Instituto de Salud Carlos III (AC18/00107 and PI2/01262 M.d.l.F.) grants, both part of the ERA-NET EURONANOMED III project PANIPAC (grant number JTC2018/041), and FIS grants PI18/00757 and PI21/01110 (B.S.,Jr.), all co-financed through the European Regional Development Fund (FEDER) “Una manera de hacer Europa”; a Coordinated grant (GC16173694BARB; B.S.,Jr.) from the Fundación Asociación Española Contra el Cáncer (AECC); and a Max Eder Fellowship of the German Cancer Aid (111746) (P.C.H.). This study was also supported by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria (IN607B2021/14 M.d.l.F.). A.P.-C. was supported by a Juan de la Cierva Formación Fellowship (FJC2020-044220-I). M.A.-S was supported by an IDIS Predoctoral Fellowship. J.C.L.-G. received support from a 'la Caixa' Foundation (ID 100010434) fellowship (LCF/BQ/DR21/11880011) and an EMBO Scientific Exchange Fellowship (ID 10210).Peer reviewedBioMed CentralConferencia de Rectores de las Universidades EspañolasConsejo Superior de Investigaciones Científicas (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Instituto de Salud Carlos IIIEuropean CommissionFundación Científica Asociación Española Contra el CáncerGerman Cancer AidAxencia Galega de InnovaciónFundación la CaixaEMBOConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/383804reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCI2019-103725https://doi.org/10.1186/s12951-024-03010-5Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3838042026-05-22T06:33:51Z
score 15,811543

Similar Items