Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer
Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effec...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087623000545 |
| _version_ | 1797689506383527936 |
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| author | Ying Zhang Hao Pan Changxiang Yu Rui Liu Bin Xing Bei Jia Jiachen He Xintao Jia Xiaojiao Feng Qingqing Zhang Wenli Dang Zheming Hu Xiuping Deng Pan Guo Zhidong Liu Weisan Pan |
| author_facet | Ying Zhang Hao Pan Changxiang Yu Rui Liu Bin Xing Bei Jia Jiachen He Xintao Jia Xiaojiao Feng Qingqing Zhang Wenli Dang Zheming Hu Xiuping Deng Pan Guo Zhidong Liu Weisan Pan |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors. |
| first_indexed | 2024-03-12T01:47:31Z |
| format | Article |
| id | doaj.art-7eba17fcbf8f496da28197ac555aa5ff |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-03-12T01:47:31Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-7eba17fcbf8f496da28197ac555aa5ff2023-09-09T04:54:53ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762023-07-01184100827Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancerYing Zhang0Hao Pan1Changxiang Yu2Rui Liu3Bin Xing4Bei Jia5Jiachen He6Xintao Jia7Xiaojiao Feng8Qingqing Zhang9Wenli Dang10Zheming Hu11Xiuping Deng12Pan Guo13Zhidong Liu14Weisan Pan15State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaSchool of Pharmacy, Liaoning University, Shenyang 110036, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Corresponding authors.School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding authors.Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.http://www.sciencedirect.com/science/article/pii/S1818087623000545PhytoestrogenTanshinone IIADoxorubicinBreast cancerTargeting delivery |
| spellingShingle | Ying Zhang Hao Pan Changxiang Yu Rui Liu Bin Xing Bei Jia Jiachen He Xintao Jia Xiaojiao Feng Qingqing Zhang Wenli Dang Zheming Hu Xiuping Deng Pan Guo Zhidong Liu Weisan Pan Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer Asian Journal of Pharmaceutical Sciences Phytoestrogen Tanshinone IIA Doxorubicin Breast cancer Targeting delivery |
| title | Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer |
| title_full | Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer |
| title_fullStr | Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer |
| title_full_unstemmed | Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer |
| title_short | Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer |
| title_sort | phytoestrogen derived multifunctional ligands for targeted therapy of breast cancer |
| topic | Phytoestrogen Tanshinone IIA Doxorubicin Breast cancer Targeting delivery |
| url | http://www.sciencedirect.com/science/article/pii/S1818087623000545 |
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