TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors

Songlin Song,1,2 Lin Gui,1,2 Qiqi Feng,1,2 Ayijiang Taledaohan,1,2 Yuanming Li,3 Wei Wang,4 Yanming Wang,5 Yuji Wang1,2 1School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of China; 2Beijing Area Major Laboratory of Peptide and Small Molecula...

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Autores principales:	Song S, Gui L, Feng Q, Taledaohan A, Li Y, Wang W, Wang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	au nanoparticle transmembrane peptide pad4 inhibitor anti-tumor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/84efe1fdcd6448caa7bcf11ed451d701
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spelling	oai:doaj.org-article:84efe1fdcd6448caa7bcf11ed451d7012021-12-02T06:38:37ZTAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors1178-2013https://doaj.org/article/84efe1fdcd6448caa7bcf11ed451d7012020-09-01T00:00:00Zhttps://www.dovepress.com/tat-modified-gold-nanoparticles-enhance-the-antitumor-activity-of-pad4-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Songlin Song,1,2 Lin Gui,1,2 Qiqi Feng,1,2 Ayijiang Taledaohan,1,2 Yuanming Li,3 Wei Wang,4 Yanming Wang,5 Yuji Wang1,2 1School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing 100069, People’s Republic of China; 3Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 4Department of Chemistry, University of Bergen, Bergen, Norway; 5School of Life Sciences, Henan University, Kaifeng 475004, People’s Republic of ChinaCorrespondence: Yuji WangSchool of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of ChinaTel +86 10 83950236Email wangyuji@ccmu.edu.cnPurpose: Histone citrullination by peptidylarginine deiminases 4 (PAD4) regulates the gene expression of tumor suppressor. In our previously study, YW3-56 (356) was developed as a potent PAD4 inhibitor for cancer therapy with novel function in the autophagy pathway. To enhance the antitumor activity, the PAD4 inhibitor 356 was modified by the well-established cationic penetrating peptide RKKRRQRRR (peptide TAT) and gold nanoparticles to obtain 356-TAT-AuNPs which could enhance the permeability of chemical drug in solid tumor.Methods: 356-TAT-AuNPs were prepared, and their morphology were characterized. The antitumor activity of 356-TAT-AuNPs was evaluated in vitro and in vivo.Results: 356-TAT-AuNPs exhibited higher anticancer activity against HCT-116, MCF-7 and A549 cells than 356 and 356-AuNPs. Compared with 356 and 356-AuNPs, 356-TAT-AuNPs entered the cytoplasm and nuclear, exhibited stronger anticancer activity by increasing apoptosis, inducing autophagy and inhibiting of histone H3 citrullination, and in HCT-116 xenograft mouse model, 356-TAT-AuNPs could improve the antitumor activity.Conclusion: The modified AuNPs with peptide TAT as drug delivery system are potent in delaying tumor growth and could be a powerful vehicle for profitable anticancer drug development. We believe that peptide TAT modification strategy may provide a simple and valuable method for improving antitumor activity of PAD4 inhibitors for clinical use.Keywords: Au nanoparticle, transmembrane peptide, PAD4 inhibitor, antitumorSong SGui LFeng QTaledaohan ALi YWang WWang YWang YDove Medical Pressarticleau nanoparticletransmembrane peptidepad4 inhibitoranti-tumorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6659-6671 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	au nanoparticle transmembrane peptide pad4 inhibitor anti-tumor Medicine (General) R5-920
spellingShingle	au nanoparticle transmembrane peptide pad4 inhibitor anti-tumor Medicine (General) R5-920 Song S Gui L Feng Q Taledaohan A Li Y Wang W Wang Y Wang Y TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
description	Songlin Song,1,2 Lin Gui,1,2 Qiqi Feng,1,2 Ayijiang Taledaohan,1,2 Yuanming Li,3 Wei Wang,4 Yanming Wang,5 Yuji Wang1,2 1School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing 100069, People’s Republic of China; 3Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 4Department of Chemistry, University of Bergen, Bergen, Norway; 5School of Life Sciences, Henan University, Kaifeng 475004, People’s Republic of ChinaCorrespondence: Yuji WangSchool of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of ChinaTel +86 10 83950236Email wangyuji@ccmu.edu.cnPurpose: Histone citrullination by peptidylarginine deiminases 4 (PAD4) regulates the gene expression of tumor suppressor. In our previously study, YW3-56 (356) was developed as a potent PAD4 inhibitor for cancer therapy with novel function in the autophagy pathway. To enhance the antitumor activity, the PAD4 inhibitor 356 was modified by the well-established cationic penetrating peptide RKKRRQRRR (peptide TAT) and gold nanoparticles to obtain 356-TAT-AuNPs which could enhance the permeability of chemical drug in solid tumor.Methods: 356-TAT-AuNPs were prepared, and their morphology were characterized. The antitumor activity of 356-TAT-AuNPs was evaluated in vitro and in vivo.Results: 356-TAT-AuNPs exhibited higher anticancer activity against HCT-116, MCF-7 and A549 cells than 356 and 356-AuNPs. Compared with 356 and 356-AuNPs, 356-TAT-AuNPs entered the cytoplasm and nuclear, exhibited stronger anticancer activity by increasing apoptosis, inducing autophagy and inhibiting of histone H3 citrullination, and in HCT-116 xenograft mouse model, 356-TAT-AuNPs could improve the antitumor activity.Conclusion: The modified AuNPs with peptide TAT as drug delivery system are potent in delaying tumor growth and could be a powerful vehicle for profitable anticancer drug development. We believe that peptide TAT modification strategy may provide a simple and valuable method for improving antitumor activity of PAD4 inhibitors for clinical use.Keywords: Au nanoparticle, transmembrane peptide, PAD4 inhibitor, antitumor
format	article
author	Song S Gui L Feng Q Taledaohan A Li Y Wang W Wang Y Wang Y
author_facet	Song S Gui L Feng Q Taledaohan A Li Y Wang W Wang Y Wang Y
author_sort	Song S
title	TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
title_short	TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
title_full	TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
title_fullStr	TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
title_full_unstemmed	TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
title_sort	tat-modified gold nanoparticles enhance the antitumor activity of pad4 inhibitors
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/84efe1fdcd6448caa7bcf11ed451d701
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TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors

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