Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/34745 |
Resumo: | Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic 3D micro-spheroids for evaluating MSCs-solid tumors interactions and screen advanced nano-in-MSCs therapies. Breast cancer monotypic and heterotypic models comprising cancer cells and cancer associated fibroblasts (CAFs) were self-assembled under controlled conditions using the liquid overlay technique. The resulting microtumors exhibited high compactness, reproducible morphology and necrotic regions, similarly to native solid tumors. For evaluating tumoritropic therapies in organotypic tumor-stroma 3D models, theranostic polydopamine nanoparticles loaded with indocyanine green-doxorubicin combinations (PDA-ICG-DOX) were synthesized and administered to human bone-marrow derived MSCs (hBM-MSCs). The dual-loaded PDA nano-platforms were efficiently internalized, exhibited highly efficient NIR-light responsivity and assured MSCs viability up to 3 days. The administration of PDA-ICG-DOX nano-in-MSC tumoritropic units to microtumor models was performed in ultra-low adhesion surfaces for simulating in vitro the stem cell-tumor interactions observed in the in vivo scenario. Bioimaging analysis revealed hBM-MSCs adhesion to 3D cancer cells mass and MSCs-chemo-photothermal nanotherapeutics exhibited higher anti-tumor potential when compared to their standalone chemotherapy treated 3D tumor counterparts. Overall, the proposed methodology is suitable for evaluating MSCs-microtumors individualized interactions and enables a rapid high-throughput screening of tumoritropic therapies bioperformance. |
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Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids3D tumor modelsCell NanotherapiesChemo-Photothermal therapyIn vitro screeningLiving therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic 3D micro-spheroids for evaluating MSCs-solid tumors interactions and screen advanced nano-in-MSCs therapies. Breast cancer monotypic and heterotypic models comprising cancer cells and cancer associated fibroblasts (CAFs) were self-assembled under controlled conditions using the liquid overlay technique. The resulting microtumors exhibited high compactness, reproducible morphology and necrotic regions, similarly to native solid tumors. For evaluating tumoritropic therapies in organotypic tumor-stroma 3D models, theranostic polydopamine nanoparticles loaded with indocyanine green-doxorubicin combinations (PDA-ICG-DOX) were synthesized and administered to human bone-marrow derived MSCs (hBM-MSCs). The dual-loaded PDA nano-platforms were efficiently internalized, exhibited highly efficient NIR-light responsivity and assured MSCs viability up to 3 days. The administration of PDA-ICG-DOX nano-in-MSC tumoritropic units to microtumor models was performed in ultra-low adhesion surfaces for simulating in vitro the stem cell-tumor interactions observed in the in vivo scenario. Bioimaging analysis revealed hBM-MSCs adhesion to 3D cancer cells mass and MSCs-chemo-photothermal nanotherapeutics exhibited higher anti-tumor potential when compared to their standalone chemotherapy treated 3D tumor counterparts. Overall, the proposed methodology is suitable for evaluating MSCs-microtumors individualized interactions and enables a rapid high-throughput screening of tumoritropic therapies bioperformance.Elsevier2022-09-22T12:48:28Z2021-01-01T00:00:00Z2021-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/34745eng0168-365910.1016/j.jconrel.2020.12.054Ferreira, Luís P.Gaspar, Vítor M.Monteiro, Maria V.Freitas, BrunoSilva, Nuno J. O.Mano, João F.info: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:RCAAP2024-02-22T12:07:17Zoai:ria.ua.pt:10773/34745Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:06:04.570506Repositório 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 |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
title |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
spellingShingle |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids Ferreira, Luís P. 3D tumor models Cell Nanotherapies Chemo-Photothermal therapy In vitro screening |
title_short |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
title_full |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
title_fullStr |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
title_full_unstemmed |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
title_sort |
Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids |
author |
Ferreira, Luís P. |
author_facet |
Ferreira, Luís P. Gaspar, Vítor M. Monteiro, Maria V. Freitas, Bruno Silva, Nuno J. O. Mano, João F. |
author_role |
author |
author2 |
Gaspar, Vítor M. Monteiro, Maria V. Freitas, Bruno Silva, Nuno J. O. Mano, João F. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Ferreira, Luís P. Gaspar, Vítor M. Monteiro, Maria V. Freitas, Bruno Silva, Nuno J. O. Mano, João F. |
dc.subject.por.fl_str_mv |
3D tumor models Cell Nanotherapies Chemo-Photothermal therapy In vitro screening |
topic |
3D tumor models Cell Nanotherapies Chemo-Photothermal therapy In vitro screening |
description |
Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic 3D micro-spheroids for evaluating MSCs-solid tumors interactions and screen advanced nano-in-MSCs therapies. Breast cancer monotypic and heterotypic models comprising cancer cells and cancer associated fibroblasts (CAFs) were self-assembled under controlled conditions using the liquid overlay technique. The resulting microtumors exhibited high compactness, reproducible morphology and necrotic regions, similarly to native solid tumors. For evaluating tumoritropic therapies in organotypic tumor-stroma 3D models, theranostic polydopamine nanoparticles loaded with indocyanine green-doxorubicin combinations (PDA-ICG-DOX) were synthesized and administered to human bone-marrow derived MSCs (hBM-MSCs). The dual-loaded PDA nano-platforms were efficiently internalized, exhibited highly efficient NIR-light responsivity and assured MSCs viability up to 3 days. The administration of PDA-ICG-DOX nano-in-MSC tumoritropic units to microtumor models was performed in ultra-low adhesion surfaces for simulating in vitro the stem cell-tumor interactions observed in the in vivo scenario. Bioimaging analysis revealed hBM-MSCs adhesion to 3D cancer cells mass and MSCs-chemo-photothermal nanotherapeutics exhibited higher anti-tumor potential when compared to their standalone chemotherapy treated 3D tumor counterparts. Overall, the proposed methodology is suitable for evaluating MSCs-microtumors individualized interactions and enables a rapid high-throughput screening of tumoritropic therapies bioperformance. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01T00:00:00Z 2021-01-01 2022-09-22T12:48:28Z |
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/10773/34745 |
url |
http://hdl.handle.net/10773/34745 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0168-3659 10.1016/j.jconrel.2020.12.054 |
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.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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 |
repository.mail.fl_str_mv |
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1799137715813351424 |