Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome

Chul-Kyu Park,1,* Yong Ho Kim,1,* Suhyun Hwangbo,2 Hoonsung Cho2 1Department of Physiology, College of Medicine, Gachon University, Incheon, 2School of Materials Science & Engineering, Chonnam National University, Gwangju, South Korea *These authors contributed equally to this wor...

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Autores principales:	Park CK, Kim YH, Hwangbo SH, Cho HS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Photodynamic therapy Rhodamine Protamine Endocytosis Cell-penetrating peptide Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b175f8f4476c4a1e86564cf47dd8253b
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spelling	oai:doaj.org-article:b175f8f4476c4a1e86564cf47dd8253b2021-12-02T05:02:11ZPhotodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome1178-2013https://doaj.org/article/b175f8f4476c4a1e86564cf47dd8253b2017-11-01T00:00:00Zhttps://www.dovepress.com/photodynamic-therapy-by-conjugation-of-cell-penetrating-peptide-with-f-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chul-Kyu Park,1,* Yong Ho Kim,1,* Suhyun Hwangbo,2 Hoonsung Cho2 1Department of Physiology, College of Medicine, Gachon University, Incheon, 2School of Materials Science & Engineering, Chonnam National University, Gwangju, South Korea *These authors contributed equally to this work Abstract: Photodynamic therapy (PDT) is a promising alternative therapy that could be used as an adjunct to chemotherapy and surgery for cancer, and works by destroying tissue with visible light in the presence of a photosensitizer (PS) and oxygen. The PS should restrict tissue destruction only to the tumor and be activated by light of a specific wavelength; both of these properties are required. Arginine-rich peptides, such as cell-penetrating peptides, have membrane-translocating and nuclear-localizing activities, which have led to their application in various drug delivery modalities. Protamine (Pro) is an arginine-rich peptide with membrane-translocating and nuclear-localizing properties. The reaction of an N-hydroxysuccinimide (NHS) ester of rhodamine (Rho) and clinical Pro was carried out in this study to yield RhoPro, and a demonstration of its phototoxicity, wherein clinical Pro improved the effect of PDT, was performed. The reaction between Pro and the NHS ester of Rho is a solution-phase reaction that results in the complete modification of the Pro peptides, which feature a single reactive amine at the N-terminal proline and a single carboxyl group at the C-terminal arginine. This study aimed to identify a new type of PS for PDT by in vitro and in vivo experiments and to assess the antitumor effects of PDT, using the Pro-conjugated PS, on a cancer cell line. Photodynamic cell death studies showed that the RhoPro produced has more efficient photodynamic activities than Rho alone, causing rapid light-induced cell death. The attachment of clinical Pro to Rho, yielding RhoPro, confers the membrane-internalizing activity of its arginine-rich content on the fluorochrome Rho and can induce rapid photodynamic cell death, presumably owing to light-induced cell membrane rupture. PDT using RhoPro for HT-29 cells was very effective and these findings suggest that RhoPro is a suitable candidate as a PS for solid tumors. Keywords: photodynamic therapy, rhodamine, protamine, endocytosis, cell-penetrating peptidePark CKKim YHHwangbo SHCho HSDove Medical PressarticlePhotodynamic therapyRhodamineProtamineEndocytosisCell-penetrating peptideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8185-8196 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Photodynamic therapy Rhodamine Protamine Endocytosis Cell-penetrating peptide Medicine (General) R5-920
spellingShingle	Photodynamic therapy Rhodamine Protamine Endocytosis Cell-penetrating peptide Medicine (General) R5-920 Park CK Kim YH Hwangbo SH Cho HS Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
description	Chul-Kyu Park,1,* Yong Ho Kim,1,* Suhyun Hwangbo,2 Hoonsung Cho2 1Department of Physiology, College of Medicine, Gachon University, Incheon, 2School of Materials Science & Engineering, Chonnam National University, Gwangju, South Korea *These authors contributed equally to this work Abstract: Photodynamic therapy (PDT) is a promising alternative therapy that could be used as an adjunct to chemotherapy and surgery for cancer, and works by destroying tissue with visible light in the presence of a photosensitizer (PS) and oxygen. The PS should restrict tissue destruction only to the tumor and be activated by light of a specific wavelength; both of these properties are required. Arginine-rich peptides, such as cell-penetrating peptides, have membrane-translocating and nuclear-localizing activities, which have led to their application in various drug delivery modalities. Protamine (Pro) is an arginine-rich peptide with membrane-translocating and nuclear-localizing properties. The reaction of an N-hydroxysuccinimide (NHS) ester of rhodamine (Rho) and clinical Pro was carried out in this study to yield RhoPro, and a demonstration of its phototoxicity, wherein clinical Pro improved the effect of PDT, was performed. The reaction between Pro and the NHS ester of Rho is a solution-phase reaction that results in the complete modification of the Pro peptides, which feature a single reactive amine at the N-terminal proline and a single carboxyl group at the C-terminal arginine. This study aimed to identify a new type of PS for PDT by in vitro and in vivo experiments and to assess the antitumor effects of PDT, using the Pro-conjugated PS, on a cancer cell line. Photodynamic cell death studies showed that the RhoPro produced has more efficient photodynamic activities than Rho alone, causing rapid light-induced cell death. The attachment of clinical Pro to Rho, yielding RhoPro, confers the membrane-internalizing activity of its arginine-rich content on the fluorochrome Rho and can induce rapid photodynamic cell death, presumably owing to light-induced cell membrane rupture. PDT using RhoPro for HT-29 cells was very effective and these findings suggest that RhoPro is a suitable candidate as a PS for solid tumors. Keywords: photodynamic therapy, rhodamine, protamine, endocytosis, cell-penetrating peptide
format	article
author	Park CK Kim YH Hwangbo SH Cho HS
author_facet	Park CK Kim YH Hwangbo SH Cho HS
author_sort	Park CK
title	Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
title_short	Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
title_full	Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
title_fullStr	Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
title_full_unstemmed	Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
title_sort	photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/b175f8f4476c4a1e86564cf47dd8253b
work_keys_str_mv	AT parkck photodynamictherapybyconjugationofcellpenetratingpeptidewithfluorochrome AT kimyh photodynamictherapybyconjugationofcellpenetratingpeptidewithfluorochrome AT hwangbosh photodynamictherapybyconjugationofcellpenetratingpeptidewithfluorochrome AT chohs photodynamictherapybyconjugationofcellpenetratingpeptidewithfluorochrome
_version_	1718400787495780352

Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome

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