Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue

Jinhui Ser1 ,* Ji Yeon Lee2 ,* Yong Ho Kim,3 Hoonsung Cho1 1School of Materials Science & Engineering, Chonnam National University, Gwangju 61186, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea; 3Gac...

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Autores principales:	Ser J, Lee JY, Kim YH, Cho H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	methylene blue protamine cpp photodynamic therapy bioconjugation anticancer fluorescent Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fc7384f54508485bbf0a52b4963756ab
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spelling	oai:doaj.org-article:fc7384f54508485bbf0a52b4963756ab2021-12-02T10:17:06ZEnhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue1178-2013https://doaj.org/article/fc7384f54508485bbf0a52b4963756ab2020-08-01T00:00:00Zhttps://www.dovepress.com/enhanced-efficacy-of-photodynamic-therapy-by-coupling-a-cell-penetrati-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jinhui Ser1 ,* Ji Yeon Lee2 ,* Yong Ho Kim,3 Hoonsung Cho1 1School of Materials Science & Engineering, Chonnam National University, Gwangju 61186, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea; 3Gachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong Ho KimGachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of KoreaTel +82-32-899-6691Fax +82-32-724-9071Email euro16@gachon.ac.krHoonsung ChoSchool of Materials Science & Engineering, Chonnam National University, Gwangju 61186, Republic of KoreaTel +82-62-530-1717Fax +82-62-530-1699Email cho.hoonsung@jnu.ac.krIntroduction: Photodynamic therapy (PDT), which induces tissue damage by exposing tissue to a specific wavelength of light in the presence of a photosensitizer and oxygen, is a promising alternative treatment that could be used as an adjunct to chemotherapy and surgery in oncology. Cell-penetrating peptides (CPPs) with high arginine content, such as protamine, have membrane translocation and lysosome localization activities. They have been used in an extensive range of drug delivery applications.Methods: We conjugated cell-penetrating peptides (CPPs) with methylene blue (MB) and then purification by FPLC. Synthesis structure was characterized by the absorbance spectrum, FPLC, Maldi-TOF, and then evaluated cell viability by cytotoxicity assay after photodynamic therapy (PDT) assay. An uptake imaging assay was used to determine the sites of MB and MB-Pro in subcellular compartments.Results: In vitro assays showed that MB-Pro has more efficient photodynamic activities than MB alone for the colon cancer cells, owing to lysosome rupture causing the rapid necrotic cell death. In this study, we coupled protamine with MB for high efficacy PDT. The conjugates localized in the lysosomes and enhanced the efficiency of PDT by inducing necrotic cell death, whereas PDT with non-coupled MB resulted in only apoptotic processes.Discussion: Our research aimed to enhance PDT by engineering the photosensitizers using CPPs coupled with methylene blue (MB). MB alone permeates through the cell membrane and distributes into the cytoplasm, whereas coupling of MB dye with CPPs localizes the MB through an endocytic mechanism to a specific organelle where the localized conjugates enhance the generation of reactive oxygen species (ROS) and induce cell damage.Keywords: methylene blue, protamine, CPP, photodynamic therapy, bioconjugation, anticancer, fluorescentSer JLee JYKim YHCho HDove Medical Pressarticlemethylene blueprotaminecppphotodynamic therapybioconjugationanticancerfluorescentMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 5803-5811 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	methylene blue protamine cpp photodynamic therapy bioconjugation anticancer fluorescent Medicine (General) R5-920
spellingShingle	methylene blue protamine cpp photodynamic therapy bioconjugation anticancer fluorescent Medicine (General) R5-920 Ser J Lee JY Kim YH Cho H Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue
description	Jinhui Ser1 ,* Ji Yeon Lee2 ,* Yong Ho Kim,3 Hoonsung Cho1 1School of Materials Science & Engineering, Chonnam National University, Gwangju 61186, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea; 3Gachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong Ho KimGachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of KoreaTel +82-32-899-6691Fax +82-32-724-9071Email euro16@gachon.ac.krHoonsung ChoSchool of Materials Science & Engineering, Chonnam National University, Gwangju 61186, Republic of KoreaTel +82-62-530-1717Fax +82-62-530-1699Email cho.hoonsung@jnu.ac.krIntroduction: Photodynamic therapy (PDT), which induces tissue damage by exposing tissue to a specific wavelength of light in the presence of a photosensitizer and oxygen, is a promising alternative treatment that could be used as an adjunct to chemotherapy and surgery in oncology. Cell-penetrating peptides (CPPs) with high arginine content, such as protamine, have membrane translocation and lysosome localization activities. They have been used in an extensive range of drug delivery applications.Methods: We conjugated cell-penetrating peptides (CPPs) with methylene blue (MB) and then purification by FPLC. Synthesis structure was characterized by the absorbance spectrum, FPLC, Maldi-TOF, and then evaluated cell viability by cytotoxicity assay after photodynamic therapy (PDT) assay. An uptake imaging assay was used to determine the sites of MB and MB-Pro in subcellular compartments.Results: In vitro assays showed that MB-Pro has more efficient photodynamic activities than MB alone for the colon cancer cells, owing to lysosome rupture causing the rapid necrotic cell death. In this study, we coupled protamine with MB for high efficacy PDT. The conjugates localized in the lysosomes and enhanced the efficiency of PDT by inducing necrotic cell death, whereas PDT with non-coupled MB resulted in only apoptotic processes.Discussion: Our research aimed to enhance PDT by engineering the photosensitizers using CPPs coupled with methylene blue (MB). MB alone permeates through the cell membrane and distributes into the cytoplasm, whereas coupling of MB dye with CPPs localizes the MB through an endocytic mechanism to a specific organelle where the localized conjugates enhance the generation of reactive oxygen species (ROS) and induce cell damage.Keywords: methylene blue, protamine, CPP, photodynamic therapy, bioconjugation, anticancer, fluorescent
format	article
author	Ser J Lee JY Kim YH Cho H
author_facet	Ser J Lee JY Kim YH Cho H
author_sort	Ser J
title	Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue
title_short	Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue
title_full	Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue
title_fullStr	Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue
title_full_unstemmed	Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue
title_sort	enhanced efficacy of photodynamic therapy by coupling a cell-penetrating peptide with methylene blue
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/fc7384f54508485bbf0a52b4963756ab
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Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue

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