Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention

Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of <i>Clostridium perfringens</i> enterotoxin (C-CPE) efficiently binds several claudins. In this study, recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has b...

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Main Authors: Suhayla Alnajjar, Ingo Nolte, Annegret Becker, Jan Torben Schille, Nares Trakooljul, Marcus Frank, Anaclet Ngezahayo, Hugo Murua Escobar
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/22/12289
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author Suhayla Alnajjar
Ingo Nolte
Annegret Becker
Jan Torben Schille
Nares Trakooljul
Marcus Frank
Anaclet Ngezahayo
Hugo Murua Escobar
author_facet Suhayla Alnajjar
Ingo Nolte
Annegret Becker
Jan Torben Schille
Nares Trakooljul
Marcus Frank
Anaclet Ngezahayo
Hugo Murua Escobar
author_sort Suhayla Alnajjar
collection DOAJ
description Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of <i>Clostridium perfringens</i> enterotoxin (C-CPE) efficiently binds several claudins. In this study, recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has been used for prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) cell killing in vitro using gold-nanoparticle-mediated laser perforation (GNOME-LP). A PAC and TCC cell lines, as well as red fluorescence variants, allowing deep tissue imaging, were used. CLDN-3, -4, and -7 expression was confirmed by qPCR and immunofluorescences. The binding of C-CPE-AuNPs complexes on the cell surface was examined by scanning electron microscopy (SEM). Further, transcriptome analysis was carried out to evaluate the effect of C-CPE binder on the biological response of treated cells. Directed C-CPE-AuNP binding verified the capability to target CLDN receptors. Transcriptome analysis showed that C-CPE binding may activate immune and inflammatory responses but does not directly affect cell survival. Cancer cells ablation was demonstrated using a combination of GNOME-LP and C-CPE-AuNPs treatment reducing tumor cell viability to less than 10% depending on cell line. The fluorescent cell lines and the verified proof of concept in vitro provide the basis for perspective xenograft studies in an animal model.
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spelling doaj.art-0e116d1d8c1843d6b0d3ee07971c7aac2023-11-22T23:39:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221228910.3390/ijms222212289Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser InterventionSuhayla Alnajjar0Ingo Nolte1Annegret Becker2Jan Torben Schille3Nares Trakooljul4Marcus Frank5Anaclet Ngezahayo6Hugo Murua Escobar7Small Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, GermanySmall Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyInstitute of Cell Biology and Biophysics, Leibniz University Hannover, 30419 Hannover, GermanySmall Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, GermanyResearch Institute for Farm Animal Biology (FBN), Institute of Genome Biology, 18196 Dummerstorf, GermanyDivision of Medicine, Medical Biology and Electron Microscopy Centre, University of Rostock, 18057 Rostock, GermanyInstitute of Cell Biology and Biophysics, Leibniz University Hannover, 30419 Hannover, GermanyDivision of Medicine, Haematology, Oncology and Palliative Medicine, University of Rostock, 18057 Rostock, GermanyClaudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of <i>Clostridium perfringens</i> enterotoxin (C-CPE) efficiently binds several claudins. In this study, recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has been used for prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) cell killing in vitro using gold-nanoparticle-mediated laser perforation (GNOME-LP). A PAC and TCC cell lines, as well as red fluorescence variants, allowing deep tissue imaging, were used. CLDN-3, -4, and -7 expression was confirmed by qPCR and immunofluorescences. The binding of C-CPE-AuNPs complexes on the cell surface was examined by scanning electron microscopy (SEM). Further, transcriptome analysis was carried out to evaluate the effect of C-CPE binder on the biological response of treated cells. Directed C-CPE-AuNP binding verified the capability to target CLDN receptors. Transcriptome analysis showed that C-CPE binding may activate immune and inflammatory responses but does not directly affect cell survival. Cancer cells ablation was demonstrated using a combination of GNOME-LP and C-CPE-AuNPs treatment reducing tumor cell viability to less than 10% depending on cell line. The fluorescent cell lines and the verified proof of concept in vitro provide the basis for perspective xenograft studies in an animal model.https://www.mdpi.com/1422-0067/22/22/12289cell linesprostate cancerC-CPEgold nanoparticleGNOME-LP
spellingShingle Suhayla Alnajjar
Ingo Nolte
Annegret Becker
Jan Torben Schille
Nares Trakooljul
Marcus Frank
Anaclet Ngezahayo
Hugo Murua Escobar
Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention
International Journal of Molecular Sciences
cell lines
prostate cancer
C-CPE
gold nanoparticle
GNOME-LP
title Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention
title_full Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention
title_fullStr Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention
title_full_unstemmed Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention
title_short Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention
title_sort ablation of red stable transfected claudin expressing canine prostate adenocarcinoma and transitional cell carcinoma cell lines by c cpe gold nanoparticle mediated laser intervention
topic cell lines
prostate cancer
C-CPE
gold nanoparticle
GNOME-LP
url https://www.mdpi.com/1422-0067/22/22/12289
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