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Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells
Breast cancer in women is one of the most common life-threatening malignancies. Despite of the development for the improved treatment, there are still many limitations to overcome. Among them, cancer stem cells (CSCs) are well known for tumor formation, development, cellular heterogeneity, and cance...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821020/ https://www.ncbi.nlm.nih.gov/pubmed/36614128 http://dx.doi.org/10.3390/ijms24010685 |
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author | Koh, Eun-Young Kim, Keun-Sik Park, Hee-Bin Kim, Jong-Seok Kim, Pyung-Hwan |
author_facet | Koh, Eun-Young Kim, Keun-Sik Park, Hee-Bin Kim, Jong-Seok Kim, Pyung-Hwan |
author_sort | Koh, Eun-Young |
collection | PubMed |
description | Breast cancer in women is one of the most common life-threatening malignancies. Despite of the development for the improved treatment, there are still many limitations to overcome. Among them, cancer stem cells (CSCs) are well known for tumor formation, development, cellular heterogeneity, and cancer recurrence. Therefore, to completely cure breast cancer, treatment of both cancer and CSC is required. To selectively target CSCs, we generated a liposome-based smart nano complex using CEACAM 6 (CD66c) antibody (Ab), a novel cell-surface biomarker of breast-derived CSCs (BCSCs) discovered in our previous research. Selective and increased cellular uptake was observed in BCSCs treated with CD66c Ab-conjugated rhodamine-labeled liposomes (CDRHOL) depending on the expression level of CD66c. CD66c Ab-conjugated doxorubicin (DOX)-loaded liposomes (CDDOXL) selectively showed increased cell killing effects in BCSCs with high CD66c expression levels. In an in vivo animal study, CDRHOL showed enhanced accumulation in xenografted BCSC tumors with low delivery into non-target organs. Moreover, mice treated with CDDOXL have assessed the decreased induction ability of immune response by low expression levels of pro-inflammatory cytokines and reduced liver toxicity by histopathological analysis. Finally, the improved antitumor effect of CDDOXL was evaluated in a metastatic BCSC mouse model via systemic administration. Collectively, our study is the first to demonstrate that a multi-functional nano complex using a novel surface biomarker of BCSC may be a more effective therapeutic agent for the treatment of cancer and CSCs. |
format | Online Article Text |
id | pubmed-9821020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98210202023-01-07 Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells Koh, Eun-Young Kim, Keun-Sik Park, Hee-Bin Kim, Jong-Seok Kim, Pyung-Hwan Int J Mol Sci Article Breast cancer in women is one of the most common life-threatening malignancies. Despite of the development for the improved treatment, there are still many limitations to overcome. Among them, cancer stem cells (CSCs) are well known for tumor formation, development, cellular heterogeneity, and cancer recurrence. Therefore, to completely cure breast cancer, treatment of both cancer and CSC is required. To selectively target CSCs, we generated a liposome-based smart nano complex using CEACAM 6 (CD66c) antibody (Ab), a novel cell-surface biomarker of breast-derived CSCs (BCSCs) discovered in our previous research. Selective and increased cellular uptake was observed in BCSCs treated with CD66c Ab-conjugated rhodamine-labeled liposomes (CDRHOL) depending on the expression level of CD66c. CD66c Ab-conjugated doxorubicin (DOX)-loaded liposomes (CDDOXL) selectively showed increased cell killing effects in BCSCs with high CD66c expression levels. In an in vivo animal study, CDRHOL showed enhanced accumulation in xenografted BCSC tumors with low delivery into non-target organs. Moreover, mice treated with CDDOXL have assessed the decreased induction ability of immune response by low expression levels of pro-inflammatory cytokines and reduced liver toxicity by histopathological analysis. Finally, the improved antitumor effect of CDDOXL was evaluated in a metastatic BCSC mouse model via systemic administration. Collectively, our study is the first to demonstrate that a multi-functional nano complex using a novel surface biomarker of BCSC may be a more effective therapeutic agent for the treatment of cancer and CSCs. MDPI 2022-12-30 /pmc/articles/PMC9821020/ /pubmed/36614128 http://dx.doi.org/10.3390/ijms24010685 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Koh, Eun-Young Kim, Keun-Sik Park, Hee-Bin Kim, Jong-Seok Kim, Pyung-Hwan Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells |
title | Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells |
title_full | Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells |
title_fullStr | Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells |
title_full_unstemmed | Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells |
title_short | Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells |
title_sort | active targeting of versatile nanocomplex using the novel biomarker of breast cancer stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821020/ https://www.ncbi.nlm.nih.gov/pubmed/36614128 http://dx.doi.org/10.3390/ijms24010685 |
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