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Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy
In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767363/ https://www.ncbi.nlm.nih.gov/pubmed/33371333 http://dx.doi.org/10.3390/ijms21249764 |
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author | Jeong, Hwa Yeon Kim, Hyeri Lee, Myunghwa Hong, Jinju Lee, Joo Han Kim, Jeonghyeon Choi, Moon Jung Park, Yong Serk Kim, Sung-Chun |
author_facet | Jeong, Hwa Yeon Kim, Hyeri Lee, Myunghwa Hong, Jinju Lee, Joo Han Kim, Jeonghyeon Choi, Moon Jung Park, Yong Serk Kim, Sung-Chun |
author_sort | Jeong, Hwa Yeon |
collection | PubMed |
description | In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC and mass spectrometry. The cell-binding affinity and cytotoxicity of the conjugate were determined using confocal microscopy and WST-1 assay. The in vivo anti-tumoral efficacy of ApDC was also evaluated in mice carrying BT-474 breast tumors overexpressing HER2. The synthesized HER2-specific RNA aptamers were able to specifically and efficiently bind to HER-positive BT-474 breast cancer cells, but not to HER2-negative MDA-MB-231 breast cancer cells. Also, the HER2-specific ApDC showed strong toxicity to the target cells, BT-474, but not to MDA-MB-231 cells. According to the in vivo analyses drawn from the mouse xenografts of BT-747 tumor, the ApDC was able to more effectively inhibit the tumor growth. Compared to the control group, the mice treated with the ApDC showed a significant reduction of tumor growth. Besides, any significant body weight losses or hepatic toxicities were monitored in the ApDC-treated mice. This research suggests the HER2 aptamer-DM1 conjugate as a target-specific anti-cancer modality and provides experimental evidence supporting its enhanced effectiveness for HER2-overexpressing target tumors. This type of aptamer-conjugated anticancer drug would be utilized as a platform structure for the development of versatile targeted high-performance anticancer drugs by adopting the easy deformability and high affinity of aptamers. |
format | Online Article Text |
id | pubmed-7767363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77673632020-12-28 Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy Jeong, Hwa Yeon Kim, Hyeri Lee, Myunghwa Hong, Jinju Lee, Joo Han Kim, Jeonghyeon Choi, Moon Jung Park, Yong Serk Kim, Sung-Chun Int J Mol Sci Article In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC and mass spectrometry. The cell-binding affinity and cytotoxicity of the conjugate were determined using confocal microscopy and WST-1 assay. The in vivo anti-tumoral efficacy of ApDC was also evaluated in mice carrying BT-474 breast tumors overexpressing HER2. The synthesized HER2-specific RNA aptamers were able to specifically and efficiently bind to HER-positive BT-474 breast cancer cells, but not to HER2-negative MDA-MB-231 breast cancer cells. Also, the HER2-specific ApDC showed strong toxicity to the target cells, BT-474, but not to MDA-MB-231 cells. According to the in vivo analyses drawn from the mouse xenografts of BT-747 tumor, the ApDC was able to more effectively inhibit the tumor growth. Compared to the control group, the mice treated with the ApDC showed a significant reduction of tumor growth. Besides, any significant body weight losses or hepatic toxicities were monitored in the ApDC-treated mice. This research suggests the HER2 aptamer-DM1 conjugate as a target-specific anti-cancer modality and provides experimental evidence supporting its enhanced effectiveness for HER2-overexpressing target tumors. This type of aptamer-conjugated anticancer drug would be utilized as a platform structure for the development of versatile targeted high-performance anticancer drugs by adopting the easy deformability and high affinity of aptamers. MDPI 2020-12-21 /pmc/articles/PMC7767363/ /pubmed/33371333 http://dx.doi.org/10.3390/ijms21249764 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jeong, Hwa Yeon Kim, Hyeri Lee, Myunghwa Hong, Jinju Lee, Joo Han Kim, Jeonghyeon Choi, Moon Jung Park, Yong Serk Kim, Sung-Chun Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy |
title | Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy |
title_full | Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy |
title_fullStr | Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy |
title_full_unstemmed | Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy |
title_short | Development of HER2-Specific Aptamer-Drug Conjugate for Breast Cancer Therapy |
title_sort | development of her2-specific aptamer-drug conjugate for breast cancer therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767363/ https://www.ncbi.nlm.nih.gov/pubmed/33371333 http://dx.doi.org/10.3390/ijms21249764 |
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