Details
| Original language | English |
|---|---|
| Article number | 12289 |
| Journal | International Journal of Molecular Sciences |
| Volume | 22 |
| Issue number | 22 |
| Publication status | Published - 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.
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
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Chemistry(all)
- Spectroscopy
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Inorganic Chemistry
- Computer Science(all)
- Computer Science Applications
- Chemistry(all)
- Physical and Theoretical Chemistry
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: International Journal of Molecular Sciences, Vol. 22, No. 22, 12289, 13.11.2021.
Research output: Contribution to journal › Article › Research › peer review
}
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
UR - http://www.scopus.com/inward/record.url?scp=85118927674&partnerID=8YFLogxK
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 -