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Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis

Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the prima...

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Autores principales: Guo, Peng, Yang, Jiang, Liu, Daxing, Huang, Lan, Fell, Gillian, Huang, Jing, Moses, Marsha A., Auguste, Debra T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426465/
https://www.ncbi.nlm.nih.gov/pubmed/30906868
http://dx.doi.org/10.1126/sciadv.aav5010
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author Guo, Peng
Yang, Jiang
Liu, Daxing
Huang, Lan
Fell, Gillian
Huang, Jing
Moses, Marsha A.
Auguste, Debra T.
author_facet Guo, Peng
Yang, Jiang
Liu, Daxing
Huang, Lan
Fell, Gillian
Huang, Jing
Moses, Marsha A.
Auguste, Debra T.
author_sort Guo, Peng
collection PubMed
description Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule–1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC.
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spelling pubmed-64264652019-03-22 Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis Guo, Peng Yang, Jiang Liu, Daxing Huang, Lan Fell, Gillian Huang, Jing Moses, Marsha A. Auguste, Debra T. Sci Adv Research Articles Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule–1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC. American Association for the Advancement of Science 2019-03-20 /pmc/articles/PMC6426465/ /pubmed/30906868 http://dx.doi.org/10.1126/sciadv.aav5010 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Guo, Peng
Yang, Jiang
Liu, Daxing
Huang, Lan
Fell, Gillian
Huang, Jing
Moses, Marsha A.
Auguste, Debra T.
Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
title Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
title_full Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
title_fullStr Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
title_full_unstemmed Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
title_short Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
title_sort dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426465/
https://www.ncbi.nlm.nih.gov/pubmed/30906868
http://dx.doi.org/10.1126/sciadv.aav5010
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