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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
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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. |
format | Online Article Text |
id | pubmed-6426465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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