Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate

Tan Yang,1,* Ling Xu,1,* Bin Li,1 Weijie Li,1 Xiang Ma,1 Lingling Fan,2 Robert J Lee,3 Chuanrui Xu,1 Guangya Xiang1 1Department of Biopharmaceuticals, School of Pharmacy, 2Stem Cell Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People&a...

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Autores principales:	Yang T, Xu L, Li B, Li W, Ma X, Fan L, Lee RJ, Xu C, Xiang G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Folate Immunoglobulin G Doxorubicin antibody-drug conjugate cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fb1f3f853cf842fda2bbe22063f78726
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spelling	oai:doaj.org-article:fb1f3f853cf842fda2bbe22063f787262021-12-02T11:01:34ZAntitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate1178-2013https://doaj.org/article/fb1f3f853cf842fda2bbe22063f787262017-03-01T00:00:00Zhttps://www.dovepress.com/antitumor-activity-of-a-folate-receptor-targeted-immunoglobulin-g-doxo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tan Yang,1,* Ling Xu,1,* Bin Li,1 Weijie Li,1 Xiang Ma,1 Lingling Fan,2 Robert J Lee,3 Chuanrui Xu,1 Guangya Xiang1 1Department of Biopharmaceuticals, School of Pharmacy, 2Stem Cell Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: Development of antibody-drug conjugates (ADCs) is a promising therapeutic strategy for cancer therapy. In this study, folate was conjugated via a polyethyleneglycol (PEG) linker to immunoglobulin G (IgG), which was linked to doxorubicin (DOX), to form a novel ADC folate-PEG-IgG-DOX (FA-PEG-IgG-DOX). The FA-PEG-IgG-DOX showed high targeting efficiency in HeLa and KB cells and significantly improved the uptake and retention of DOX compared with IgG-DOX about 10-fold. Subsequently, FA-PEG-IgG-DOX was shown to have at least 8 times higher antitumor activity than IgG-DOX both in HeLa and KB cells and also induced more apoptosis in those cells than IgG-DOX. Moreover, FA-PEG-IgG-DOX had a 2 times longer circulating time than FA-IgG-DOX, but did not increase the DOX distribution in mouse hearts. Importantly, FA-PEG-IgG-DOX treatment significantly inhibited tumor growth in xenograft mice. Together, our results indicate that FA-PEG-IgG is an effective ADC carrier for delivery of chemotherapeutic agents and that conjugating tumor targeting ligands to antibodies is a promising strategy for producing ADC drugs. Keywords: folate, immunoglobulin G, doxorubicin, antibody-drug conjugate, cancerYang TXu LLi BLi WMa XFan LLee RJXu CXiang GDove Medical PressarticleFolateImmunoglobulin GDoxorubicinantibody-drug conjugatecancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2505-2515 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Folate Immunoglobulin G Doxorubicin antibody-drug conjugate cancer Medicine (General) R5-920
spellingShingle	Folate Immunoglobulin G Doxorubicin antibody-drug conjugate cancer Medicine (General) R5-920 Yang T Xu L Li B Li W Ma X Fan L Lee RJ Xu C Xiang G Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate
description	Tan Yang,1,* Ling Xu,1,* Bin Li,1 Weijie Li,1 Xiang Ma,1 Lingling Fan,2 Robert J Lee,3 Chuanrui Xu,1 Guangya Xiang1 1Department of Biopharmaceuticals, School of Pharmacy, 2Stem Cell Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: Development of antibody-drug conjugates (ADCs) is a promising therapeutic strategy for cancer therapy. In this study, folate was conjugated via a polyethyleneglycol (PEG) linker to immunoglobulin G (IgG), which was linked to doxorubicin (DOX), to form a novel ADC folate-PEG-IgG-DOX (FA-PEG-IgG-DOX). The FA-PEG-IgG-DOX showed high targeting efficiency in HeLa and KB cells and significantly improved the uptake and retention of DOX compared with IgG-DOX about 10-fold. Subsequently, FA-PEG-IgG-DOX was shown to have at least 8 times higher antitumor activity than IgG-DOX both in HeLa and KB cells and also induced more apoptosis in those cells than IgG-DOX. Moreover, FA-PEG-IgG-DOX had a 2 times longer circulating time than FA-IgG-DOX, but did not increase the DOX distribution in mouse hearts. Importantly, FA-PEG-IgG-DOX treatment significantly inhibited tumor growth in xenograft mice. Together, our results indicate that FA-PEG-IgG is an effective ADC carrier for delivery of chemotherapeutic agents and that conjugating tumor targeting ligands to antibodies is a promising strategy for producing ADC drugs. Keywords: folate, immunoglobulin G, doxorubicin, antibody-drug conjugate, cancer
format	article
author	Yang T Xu L Li B Li W Ma X Fan L Lee RJ Xu C Xiang G
author_facet	Yang T Xu L Li B Li W Ma X Fan L Lee RJ Xu C Xiang G
author_sort	Yang T
title	Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate
title_short	Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate
title_full	Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate
title_fullStr	Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate
title_full_unstemmed	Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate
title_sort	antitumor activity of a folate receptor-targeted immunoglobulin g-doxorubicin conjugate
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/fb1f3f853cf842fda2bbe22063f78726
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Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate

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