Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

Shuai Dong,1,2 Hongxi Shi,1 Xintong Zhang,1,2 Xi Chen,1 Donghui Cao,2 Chuanbin Mao,3,4 Xiang Gao,1 Li Wang1 1Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 2First Hospital of Jilin University, Changchun, Jilin, 3Sch...

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Autores principales:	Dong S, Shi H, Zhang X, Chen X, Cao D, Mao C, Gao X, Wang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PPa phage photodynamic therapy apoptosis metacaspase Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/30e48e38d98f428dac40f029e6e19f79
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spelling	oai:doaj.org-article:30e48e38d98f428dac40f029e6e19f792021-12-02T01:54:30ZDifunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation1178-2013https://doaj.org/article/30e48e38d98f428dac40f029e6e19f792018-04-01T00:00:00Zhttps://www.dovepress.com/difunctional-bacteriophage-conjugated-with-photosensitizers-for-candid-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shuai Dong,1,2 Hongxi Shi,1 Xintong Zhang,1,2 Xi Chen,1 Donghui Cao,2 Chuanbin Mao,3,4 Xiang Gao,1 Li Wang1 1Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 2First Hospital of Jilin University, Changchun, Jilin, 3School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, China; 4Department of Chemistry and Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, Norman, OK, USA Background: Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods: In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway.Results: A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans. We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis. Conclusion: PPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation. Keywords: PPA, phage, photodynamic therapy, apoptosis, metacaspaseDong SShi HZhang XChen XCao DMao CGao XWang LDove Medical PressarticlePPaphagephotodynamic therapyapoptosismetacaspaseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2199-2216 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PPa phage photodynamic therapy apoptosis metacaspase Medicine (General) R5-920
spellingShingle	PPa phage photodynamic therapy apoptosis metacaspase Medicine (General) R5-920 Dong S Shi H Zhang X Chen X Cao D Mao C Gao X Wang L Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation
description	Shuai Dong,1,2 Hongxi Shi,1 Xintong Zhang,1,2 Xi Chen,1 Donghui Cao,2 Chuanbin Mao,3,4 Xiang Gao,1 Li Wang1 1Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 2First Hospital of Jilin University, Changchun, Jilin, 3School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, China; 4Department of Chemistry and Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, Norman, OK, USA Background: Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods: In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway.Results: A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans. We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis. Conclusion: PPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation. Keywords: PPA, phage, photodynamic therapy, apoptosis, metacaspase
format	article
author	Dong S Shi H Zhang X Chen X Cao D Mao C Gao X Wang L
author_facet	Dong S Shi H Zhang X Chen X Cao D Mao C Gao X Wang L
author_sort	Dong S
title	Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation
title_short	Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation
title_full	Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation
title_fullStr	Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation
title_full_unstemmed	Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation
title_sort	difunctional bacteriophage conjugated with photosensitizers for candida albicans-targeting photodynamic inactivation
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/30e48e38d98f428dac40f029e6e19f79
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_version_	1718402825878241280

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

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