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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Autores principales: Park JY, Shin Y, Won WR, Lim C, Kim JC, Kang K, Husni P, Lee ES, Youn YS, Oh KT
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Publicado: Dove Medical Press 2021
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic tumor-targeting ligand
urokinase-type plasminogen activator
liposome
circulating tumor cell
metastatic tumor
Medicine (General)
R5-920
spellingShingle 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
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