Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma

Detalhes bibliográficos
Autor(a) principal: Khazaei Monfared, Yousef
Data de Publicação: 2023
Outros Autores: Mahmoudian, Mohammad, Zakeri-Milani, Parvin, Cecone, Claudio, Hayashi, Tomoya, Ishii, Ken J, Conde, João, Matencio, Adrián, Trotta, Francesco
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/157747
Resumo: Funding text 1 This work is the result of a contract for the University of Turin (Italy) for Training (For Y.K.M.) and for A.M. and a RTDA contract from the D.M 1062/2021 (Ministero dell’Università e della Ricerca) for the University of Turin. This research acknowledges support from the Project CH4.0 under the MIUR program “Dipartimenti di Eccellenza 2023–2027”. J.C. acknowledges that they have a contract with the European Research Council—ERC Starting Grant 848325 for financial support. Funding text 2 This research was partially funded by The Italian Ministry of Enterprises and Made in Italy (project acronym CN-RNA) under the PNRR among the initiatives aimed towards creating an integrated system of research and innovation infrastructures (PNRR M4C2 PROJECTS).
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spelling Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanomacyclodextrin-based polymerimmunotherapymelanoma cancermRNA deliverySDG 3 - Good Health and Well-beingFunding text 1 This work is the result of a contract for the University of Turin (Italy) for Training (For Y.K.M.) and for A.M. and a RTDA contract from the D.M 1062/2021 (Ministero dell’Università e della Ricerca) for the University of Turin. This research acknowledges support from the Project CH4.0 under the MIUR program “Dipartimenti di Eccellenza 2023–2027”. J.C. acknowledges that they have a contract with the European Research Council—ERC Starting Grant 848325 for financial support. Funding text 2 This research was partially funded by The Italian Ministry of Enterprises and Made in Italy (project acronym CN-RNA) under the PNRR among the initiatives aimed towards creating an integrated system of research and innovation infrastructures (PNRR M4C2 PROJECTS).mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA-OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy.Centre for Toxicogenomics and Human Health (ToxOmics)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNKhazaei Monfared, YousefMahmoudian, MohammadZakeri-Milani, ParvinCecone, ClaudioHayashi, TomoyaIshii, Ken JConde, JoãoMatencio, AdriánTrotta, Francesco2023-09-13T22:17:17Z2023-07-242023-07-24T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/157747eng2072-6694PURE: 69583482https://doi.org/10.3390/cancers15143748info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:40:02Zoai:run.unl.pt:10362/157747Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:56:50.869277Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
title Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
spellingShingle Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
Khazaei Monfared, Yousef
cyclodextrin-based polymer
immunotherapy
melanoma cancer
mRNA delivery
SDG 3 - Good Health and Well-being
title_short Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
title_full Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
title_fullStr Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
title_full_unstemmed Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
title_sort Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma
author Khazaei Monfared, Yousef
author_facet Khazaei Monfared, Yousef
Mahmoudian, Mohammad
Zakeri-Milani, Parvin
Cecone, Claudio
Hayashi, Tomoya
Ishii, Ken J
Conde, João
Matencio, Adrián
Trotta, Francesco
author_role author
author2 Mahmoudian, Mohammad
Zakeri-Milani, Parvin
Cecone, Claudio
Hayashi, Tomoya
Ishii, Ken J
Conde, João
Matencio, Adrián
Trotta, Francesco
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centre for Toxicogenomics and Human Health (ToxOmics)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Khazaei Monfared, Yousef
Mahmoudian, Mohammad
Zakeri-Milani, Parvin
Cecone, Claudio
Hayashi, Tomoya
Ishii, Ken J
Conde, João
Matencio, Adrián
Trotta, Francesco
dc.subject.por.fl_str_mv cyclodextrin-based polymer
immunotherapy
melanoma cancer
mRNA delivery
SDG 3 - Good Health and Well-being
topic cyclodextrin-based polymer
immunotherapy
melanoma cancer
mRNA delivery
SDG 3 - Good Health and Well-being
description Funding text 1 This work is the result of a contract for the University of Turin (Italy) for Training (For Y.K.M.) and for A.M. and a RTDA contract from the D.M 1062/2021 (Ministero dell’Università e della Ricerca) for the University of Turin. This research acknowledges support from the Project CH4.0 under the MIUR program “Dipartimenti di Eccellenza 2023–2027”. J.C. acknowledges that they have a contract with the European Research Council—ERC Starting Grant 848325 for financial support. Funding text 2 This research was partially funded by The Italian Ministry of Enterprises and Made in Italy (project acronym CN-RNA) under the PNRR among the initiatives aimed towards creating an integrated system of research and innovation infrastructures (PNRR M4C2 PROJECTS).
publishDate 2023
dc.date.none.fl_str_mv 2023-09-13T22:17:17Z
2023-07-24
2023-07-24T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/157747
url http://hdl.handle.net/10362/157747
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2072-6694
PURE: 69583482
https://doi.org/10.3390/cancers15143748
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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