Publisher Correction: Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Becker, Annegret; Leskau, Miriam; Schlingmann-Molina, Barbara L.; Hohmeier, Susanne C.; Alnajjar, Suhayla; Escobar, Hugo Murua; Ngezahayo, Anaclet

doi:10.1038/s41598-018-37180-8

Cited by 4 publications

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“…In the previous study, we showed that the energy power of the applied laser at 60 mJ/cm 3 and a scanning speed of 0.5 cm/s in combination with C-CPE-AuNPs reduced cell survival to less than 30% of claudin expressing cell lines [36]. In a rst experiment, GNOME-LP with the same settings accordingly reduced cell survival to about 30% in native DT0846 cells, but showed no effect on the transfected uorescence cells (data not shown).…”

Section: Discussionmentioning

confidence: 98%

“…However, studies in vivo revealed that systemic administration of full-length CPE in mice was toxic and thus limited its use to local therapies [52]. Previously we demonstrated that the noncytotoxic C-terminal domain of CPE, which preserves CPE's binding a nity to CLDN receptors, is capable to functionalize AuNPs [36]. Imaging of C-CPE binding to the canine tumor cell lines proved that the protein can speci cally target CLDN3, -4 and − 7 demonstrating that the functionalization did not alter the binding capacity to CLDN.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the AuNPs accumulation in normal cells, an undesirable damage is associated with non-targeted AuNPs [35]. In a previous study, we demonstrated that C-CPE-AuNPs can be used to speci cally and e ciently kill human colon, conventional mammary gland and esophageal adenocarcinoma cells, expressing CLDN3, -4 and − 7, using gold nanoparticle-mediated laser perforation (GNOME-LP) technique [36,37] .…”

Section: Introductionmentioning

confidence: 99%

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Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention

Alnajjar

Nolte

Becker

et al. 2021

Preprint

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Background: Claudin (CLDN) proteins have been described to be found and accordingly targeted to evaluate novel therapeutic approaches. C-terminus of Clostridium perfringens enterotoxin (C-CPE) binds efficiently several claudins and thus recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has been used for cancer cell targeting using gold nanoparticle- mediated laser perforation (GNOME-LP). Cancer cells inoculation is routinely used to generate in vivo models to evaluate novel therapeutic approaches in prostate cancer. However, detailed characterization of cancer spreading and early tumor development and therapeutic response is often limited as conventional cell lines do not allow advanced deep tissue imaging.Methods: two canine prostate cancer cell lines were stably transfected with red fluorescent protein (RFP), followed by G418 selection. RFP marker as well as CLDN3, -4 and -7 expression was comparatively confirmed by flow cytometry, qPCR and immunofluorescences. For cancer cells targeting, GNOME-LP at a laser fluence of 72 mJ/cm² and a scanning speed of 0.5 cm/s was used. Statistical analysis was performed using SAS software 7.1, Dunnett´s Multiple Comparison Test and Student´s two-sided t-test. Differences were considered statistically significant for p<0.05.Results: we established two canine prostate carcinoma cell lines, stably expressing RFP allowing perspective deep tissue imaging. Directed C-CPE-AuNP binding to native and RFP transfected cells verified the capability to specifically target CLDN receptors. Cancer cell ablation was demonstrated in vitro setting using a combination of gold nanoparticle mediated laser perforation and C-CPE-AuNPs treatment reducing tumor cell viability to less than 10 % depending on cell line. Conclusion: the results confirm that this therapeutic approach can be used efficiently to target prostate carcinoma cells carrying a marker protein allowing deep tissue imaging. The established cell lines and the verified proof of concept in vitro study provide the basis for perspective Xenograft model in vivo studies. The introduce red fluorescence enables deep tissue imaging in living animals and therefore detailed characterization of tumor growth and subsequently possible tumor ablation through C-CPE-AuNPs treatment.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention

Alnajjar

Nolte

Becker

et al. 2021

Preprint

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“…Our previous published study demonstrated that the noncytotoxic C-terminal domain of CPE, which preserves CPE's binding affinity to CLDN receptors, is capable of functionalizing AuNPs. The imaging of C-CPE binding to the canine tumor cell lines proved that the protein can specifically target CLDN-3, -4, and -7, demonstrating that the functionalization did not alter the binding capacity to CLDN [43].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study of our group confirmed that the C-CPE bound to cell lines expressing CLDN-3, -4, and -7 but was not able to target cells without CLDN-3, -4, and -7 expression. Furthermore, we demonstrated that C-CPE-AuNPs can be used to specifically and efficiently ablate different human cell lines expressing CLDN-3, -4, and -7 by gold-nanoparticle-mediated laser perforation (GNOME-LP) technique [43,44]. However, the used cell lines do not allow one to realize experimental in vivo experiments going for deep tissue imaging.…”

Section: Introductionmentioning

confidence: 99%

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

Nolte

Becker

et al. 2021

IJMS

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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.

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Development of a Theoretical Model That Predicts Optothermal Energy Conversion of Gold Metallic Nanoparticles

et al. 2020

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Gold nanoparticles (AuNPs) can be found in different shapes and sizes, which determine their chemical and physical characteristics. Physical and chemical properties of metallic NPs can be tuned by changing their shape, size, and surface chemistry; therefore, this has led to their use in a wide variety of applications in many industrial and academic sectors. One of the features of metallic NPs is their ability to act as optothermal energy converters, where they absorb light at a specific wavelength and heat up their local nanosurfaces. This feature has been used in many applications where metallic NPs get coupled with thermally responsive systems to trigger an optical response. In this study, we synthesized AuNPs that are spherical in shape with an average diameter of 20.07 nm. This work assessed simultaneously theoretical and experimental techniques to evaluate the different factors that affect heat generation at the surface of AuNPs when exposed to a specific light wavelength. The results indicated that laser power, concentration of AuNPs, time × laser power interaction, and time illumination, were the most important factors that contributed to the temperature change exhibited in the AuNPs solution. We report a regression model that allows predicting heat generation and temperature changes with residual standard errors of less than 4%. These results are highly relevant in the future design and development of applications where metallic NPs are incorporated into systems to induce a temperature change triggered by light exposure.

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Publisher Correction: Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Cited by 4 publications

References 0 publications

Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention

Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention

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

Development of a Theoretical Model That Predicts Optothermal Energy Conversion of Gold Metallic Nanoparticles

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Publisher Correction: Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique

Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Cited by 4 publications

References 0 publications

Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE&nbsp;Gold-Nanoparticle Mediated Laser Intervention

Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE&nbsp;Gold-Nanoparticle Mediated Laser Intervention

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

Development of a Theoretical Model That Predicts Optothermal Energy Conversion of Gold Metallic Nanoparticles

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Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention

Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention