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

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Suhayla Alnajjar
  • Ingo Nolte
  • Annegret Becker
  • Jan Torben Schille
  • Nares Trakooljul
  • Marcus Frank
  • Anaclet Ngezahayo
  • Hugo Murua Escobar

Externe Organisationen

  • Stiftung Tierärztliche Hochschule Hannover
  • Forschungsinstitut für Nutztierbiologie (FBN)
  • Universitätsmedizin Rostock
  • Universität Rostock
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Details

OriginalspracheEnglisch
Aufsatznummer12289
FachzeitschriftInternational Journal of Molecular Sciences
Jahrgang22
Ausgabenummer22
PublikationsstatusVeröffentlicht - 13 Nov. 2021

Abstract

Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of Clostridium perfringens 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.

ASJC Scopus Sachgebiete

Ziele für nachhaltige Entwicklung

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Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention. / Alnajjar, Suhayla; Nolte, Ingo; Becker, Annegret et al.
in: International Journal of Molecular Sciences, Jahrgang 22, Nr. 22, 12289, 13.11.2021.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Alnajjar S, Nolte I, Becker A, Schille JT, Trakooljul N, Frank M et al. 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. 2021 Nov 13;22(22):12289. doi: 10.3390/ijms222212289, 10.3390/ijms222212289
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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",
abstract = "Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of Clostridium perfringens 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.",
keywords = "Adenocarcinoma/metabolism, Animals, Carcinoma, Transitional Cell/metabolism, Cell Line, Tumor, Clostridium perfringens/chemistry, Dog Diseases/metabolism, Dogs, Enterotoxins/chemistry, Gold/chemistry, Laser Therapy, Male, Metal Nanoparticles/chemistry, Prostatic Neoplasms/metabolism, C-CPE, GNOME-LP, Cell lines, Prostate cancer, Gold nanoparticle",
author = "Suhayla Alnajjar and Ingo Nolte and Annegret Becker and Schille, {Jan Torben} and Nares Trakooljul and Marcus Frank and Anaclet Ngezahayo and {Murua Escobar}, Hugo",
note = "Funding Information: Funding: The authors wish to thank Aleppo University (Aleppo, Syria) and HGFK (Hannoversche Gesellschaft zur F{\"o}rderung der Kleintiermeidizin e.V.) (Hannover, Germany) for supporting SA with a scholarship. Acknowledgments: The authors would like to thank Alexander Heisterkamp, Institute of Quantum Optics, Leibniz University, Hannover, for cell killing data interpretation and Karoline Schulz and Armin Springer, Medical Biology and Electron Microscopy Centre, University of Rostock, for technical support during electron microscopy analysis. The publication of this article was funded by the Open Access Fund of the Leibniz Universit{\"a}t Hannover.",
year = "2021",
month = nov,
day = "13",
doi = "10.3390/ijms222212289",
language = "English",
volume = "22",
journal = "International Journal of Molecular Sciences",
issn = "1422-0067",
publisher = "Multidisciplinary Digital Publishing Institute",
number = "22",

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Download

TY - JOUR

T1 - Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention

AU - Alnajjar, Suhayla

AU - Nolte, Ingo

AU - Becker, Annegret

AU - Schille, Jan Torben

AU - Trakooljul, Nares

AU - Frank, Marcus

AU - Ngezahayo, Anaclet

AU - Murua Escobar, Hugo

N1 - Funding Information: Funding: The authors wish to thank Aleppo University (Aleppo, Syria) and HGFK (Hannoversche Gesellschaft zur Förderung der Kleintiermeidizin e.V.) (Hannover, Germany) for supporting SA with a scholarship. Acknowledgments: The authors would like to thank Alexander Heisterkamp, Institute of Quantum Optics, Leibniz University, Hannover, for cell killing data interpretation and Karoline Schulz and Armin Springer, Medical Biology and Electron Microscopy Centre, University of Rostock, for technical support during electron microscopy analysis. The publication of this article was funded by the Open Access Fund of the Leibniz Universität Hannover.

PY - 2021/11/13

Y1 - 2021/11/13

N2 - Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of Clostridium perfringens 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.

AB - Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of Clostridium perfringens 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.

KW - Adenocarcinoma/metabolism

KW - Animals

KW - Carcinoma, Transitional Cell/metabolism

KW - Cell Line, Tumor

KW - Clostridium perfringens/chemistry

KW - Dog Diseases/metabolism

KW - Dogs

KW - Enterotoxins/chemistry

KW - Gold/chemistry

KW - Laser Therapy

KW - Male

KW - Metal Nanoparticles/chemistry

KW - Prostatic Neoplasms/metabolism

KW - C-CPE

KW - GNOME-LP

KW - Cell lines

KW - Prostate cancer

KW - Gold nanoparticle

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U2 - 10.3390/ijms222212289

DO - 10.3390/ijms222212289

M3 - Article

C2 - 34830170

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 22

M1 - 12289

ER -