Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells
June Yong Park,1,* Yuseon Shin,1,* Woong Roeck Won,1 Chaemin Lim,1,2 Jae Chang Kim,1 Kioh Kang,1 Patihul Husni,1 Eun Seong Lee,3 Yu Seok Youn,4 Kyung Taek Oh1,5 1Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, Dongjak-gu, Seoul, 06974, Republic of...
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Dove Medical Press
2021
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oai:doaj.org-article:5f3cd6ca2a1d443caf62e87aaf866d622021-12-02T19:10:30ZDevelopment of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells1178-2013https://doaj.org/article/5f3cd6ca2a1d443caf62e87aaf866d622021-08-01T00:00:00Zhttps://www.dovepress.com/development-of-ae147-peptide-conjugated-nanocarriers-for-targeting-upa-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013June Yong Park,1,* Yuseon Shin,1,* Woong Roeck Won,1 Chaemin Lim,1,2 Jae Chang Kim,1 Kioh Kang,1 Patihul Husni,1 Eun Seong Lee,3 Yu Seok Youn,4 Kyung Taek Oh1,5 1Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, Dongjak-gu, Seoul, 06974, Republic of Korea; 2Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; 3Division of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, 14662, Republic of Korea; 4School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea; 5College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 06974, Republic of Korea*These authors contributed equally to this workCorrespondence: Kyung Taek OhCollege of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, 06974, Republic of KoreaTel +82-2-824-5617Email kyungoh@cau.ac.krPurpose: An AE147 peptide-conjugated nanocarrier based on PEGylated liposomes was developed in order to target the metastatic tumors overexpressing urokinase-type plasminogen activator receptor (uPAR), which cancer progression via uPA signaling. Therefore, the AE147 peptide-conjugated nanocarrier system may hold the potential for active targeting of metastatic tumors.Methods: The AE147 peptide, an antagonist of uPAR, was conjugated to the PEGylated liposomes for targeting metastatic tumors overexpressing uPAR. Docetaxel (DTX), an anticancer drug, was incorporated into the nanocarriers. The structure of the AE147-conjugated nanocarrier, its physicochemical properties, and in vivo biodistribution were evaluated.Results: The DTX-loaded nanocarrier showed a spherical structure, a high drug-loading capacity, and a high colloidal stability. Drug carrying AE147 conjugates were actively taken up by the uPAR-overexpressing MDA-MB-231 cancer cells. In vivo animal imaging confirmed that the AE147-conjugated nanoparticles effectively accumulated at the sites of tumor metastasis.Conclusion: The AE147-nanocarrier showed potential for targeting metastatic tumor cells overexpressing uPAR and as a nanomedicine platform for theragnosis applications. These results suggest that this novel nano-platform will facilitate further advancements in cancer therapy.Keywords: tumor-targeting ligand, urokinase-type plasminogen activator, liposome, circulating tumor cell, metastatic tumorPark JYShin YWon WRLim CKim JCKang KHusni PLee ESYoun YSOh KTDove Medical Pressarticletumor-targeting ligandurokinase-type plasminogen activatorliposomecirculating tumor cellmetastatic tumorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5437-5449 (2021) |
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tumor-targeting ligand urokinase-type plasminogen activator liposome circulating tumor cell metastatic tumor Medicine (General) R5-920 |
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tumor-targeting ligand urokinase-type plasminogen activator liposome circulating tumor cell metastatic tumor Medicine (General) R5-920 Park JY Shin Y Won WR Lim C Kim JC Kang K Husni P Lee ES Youn YS Oh KT Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells |
description |
June Yong Park,1,* Yuseon Shin,1,* Woong Roeck Won,1 Chaemin Lim,1,2 Jae Chang Kim,1 Kioh Kang,1 Patihul Husni,1 Eun Seong Lee,3 Yu Seok Youn,4 Kyung Taek Oh1,5 1Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, Dongjak-gu, Seoul, 06974, Republic of Korea; 2Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA; 3Division of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, 14662, Republic of Korea; 4School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea; 5College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 06974, Republic of Korea*These authors contributed equally to this workCorrespondence: Kyung Taek OhCollege of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, 06974, Republic of KoreaTel +82-2-824-5617Email kyungoh@cau.ac.krPurpose: An AE147 peptide-conjugated nanocarrier based on PEGylated liposomes was developed in order to target the metastatic tumors overexpressing urokinase-type plasminogen activator receptor (uPAR), which cancer progression via uPA signaling. Therefore, the AE147 peptide-conjugated nanocarrier system may hold the potential for active targeting of metastatic tumors.Methods: The AE147 peptide, an antagonist of uPAR, was conjugated to the PEGylated liposomes for targeting metastatic tumors overexpressing uPAR. Docetaxel (DTX), an anticancer drug, was incorporated into the nanocarriers. The structure of the AE147-conjugated nanocarrier, its physicochemical properties, and in vivo biodistribution were evaluated.Results: The DTX-loaded nanocarrier showed a spherical structure, a high drug-loading capacity, and a high colloidal stability. Drug carrying AE147 conjugates were actively taken up by the uPAR-overexpressing MDA-MB-231 cancer cells. In vivo animal imaging confirmed that the AE147-conjugated nanoparticles effectively accumulated at the sites of tumor metastasis.Conclusion: The AE147-nanocarrier showed potential for targeting metastatic tumor cells overexpressing uPAR and as a nanomedicine platform for theragnosis applications. These results suggest that this novel nano-platform will facilitate further advancements in cancer therapy.Keywords: tumor-targeting ligand, urokinase-type plasminogen activator, liposome, circulating tumor cell, metastatic tumor |
format |
article |
author |
Park JY Shin Y Won WR Lim C Kim JC Kang K Husni P Lee ES Youn YS Oh KT |
author_facet |
Park JY Shin Y Won WR Lim C Kim JC Kang K Husni P Lee ES Youn YS Oh KT |
author_sort |
Park JY |
title |
Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells |
title_short |
Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells |
title_full |
Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells |
title_fullStr |
Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells |
title_full_unstemmed |
Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells |
title_sort |
development of ae147 peptide-conjugated nanocarriers for targeting upar-overexpressing cancer cells |
publisher |
Dove Medical Press |
publishDate |
2021 |
url |
https://doaj.org/article/5f3cd6ca2a1d443caf62e87aaf866d62 |
work_keys_str_mv |
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