Details
| Original language | English |
|---|---|
| Article number | 14963 |
| Journal | Scientific reports |
| Volume | 8 |
| Publication status | Published - 8 Oct 2018 |
Abstract
A recombinant produced C-terminus of the C. perfringens enterotoxin (C-CPE) was conjugated to gold nanoparticles (AuNPs) to produce a C-CPE-AuNP complex (C-CPE-AuNP). By binding to claudins, the C- CPE should allow to target the AuNPs onto the claudin expressing tumor cells for a subsequent cell killing by application of the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. Using qPCR and immunocytochemistry, we identified the human Caco-2, MCF-7 and OE-33 as well as the canine TiHoDMglCarc1305 as tumor cells expressing claudin-3, -4 and -7. Transepithelial electrical resistance (TEER) measurements of Caco-2 cell monolayer showed that the recombinant C-CPE bound to the claudins. GNOME-LP at a laser fluence of 60 mJ/cm2 and a scanning speed of 0.5 cm/s specifically eliminated more than 75% of claudin expressing human and canine cells treated with C-CPE-AuNP. The same laser fluence did not affect the cells when non-functionalized AuNPs were used. Furthermore, most of the claudin non-expressing cells treated with C-CPE-AuNP were not killed by GNOME-LP. Additionally, application of C-CPE-AuNP to spheroids formed by MCF-7 and OE-33 cells grown in Matrigel reduced spheroid area. The results demonstrate that specific ablation of claudin expressing tumor cells is efficiently increased by activated C-CPE functionalized AuNPs using optical methods.
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In: Scientific reports, Vol. 8, 14963, 08.10.2018.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Functionalization of gold-nanoparticles by the Clostridium perfringens enterotoxin C-terminus for tumor cell ablation using the gold nanoparticle-mediated laser perforation technique
AU - Becker, Annegret
AU - Leskau, Miriam
AU - Schlingmann-Molina, Barbara L.
AU - Hohmeier, Susanne C.
AU - Alnajjar, Suhayla
AU - Escobar, Hugo Murua
AU - Ngezahayo, Anaclet
N1 - Funding Information: The authors would like to thank Dr. B. Nitzsche, Charité, Universitätsmedizin Berlin for kindly providing the OE-33 and Kyse140 cells and Prof. R. Hass, Hannover Medical School Hannover for kindly providing the MDA-MB-231 cells. Prof. Dr. Alexander Heisterkamp and Dr. Maria Leilani Torres-Mapa, Institute of Quantum Optics, Leibniz University Hannover for proof reading. The project was partly supported by DFG Transregio TR73. The publication of this article was funded by the Open Access Fund of the Leibniz Universität Hannover.
PY - 2018/10/8
Y1 - 2018/10/8
N2 - A recombinant produced C-terminus of the C. perfringens enterotoxin (C-CPE) was conjugated to gold nanoparticles (AuNPs) to produce a C-CPE-AuNP complex (C-CPE-AuNP). By binding to claudins, the C- CPE should allow to target the AuNPs onto the claudin expressing tumor cells for a subsequent cell killing by application of the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. Using qPCR and immunocytochemistry, we identified the human Caco-2, MCF-7 and OE-33 as well as the canine TiHoDMglCarc1305 as tumor cells expressing claudin-3, -4 and -7. Transepithelial electrical resistance (TEER) measurements of Caco-2 cell monolayer showed that the recombinant C-CPE bound to the claudins. GNOME-LP at a laser fluence of 60 mJ/cm2 and a scanning speed of 0.5 cm/s specifically eliminated more than 75% of claudin expressing human and canine cells treated with C-CPE-AuNP. The same laser fluence did not affect the cells when non-functionalized AuNPs were used. Furthermore, most of the claudin non-expressing cells treated with C-CPE-AuNP were not killed by GNOME-LP. Additionally, application of C-CPE-AuNP to spheroids formed by MCF-7 and OE-33 cells grown in Matrigel reduced spheroid area. The results demonstrate that specific ablation of claudin expressing tumor cells is efficiently increased by activated C-CPE functionalized AuNPs using optical methods.
AB - A recombinant produced C-terminus of the C. perfringens enterotoxin (C-CPE) was conjugated to gold nanoparticles (AuNPs) to produce a C-CPE-AuNP complex (C-CPE-AuNP). By binding to claudins, the C- CPE should allow to target the AuNPs onto the claudin expressing tumor cells for a subsequent cell killing by application of the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. Using qPCR and immunocytochemistry, we identified the human Caco-2, MCF-7 and OE-33 as well as the canine TiHoDMglCarc1305 as tumor cells expressing claudin-3, -4 and -7. Transepithelial electrical resistance (TEER) measurements of Caco-2 cell monolayer showed that the recombinant C-CPE bound to the claudins. GNOME-LP at a laser fluence of 60 mJ/cm2 and a scanning speed of 0.5 cm/s specifically eliminated more than 75% of claudin expressing human and canine cells treated with C-CPE-AuNP. The same laser fluence did not affect the cells when non-functionalized AuNPs were used. Furthermore, most of the claudin non-expressing cells treated with C-CPE-AuNP were not killed by GNOME-LP. Additionally, application of C-CPE-AuNP to spheroids formed by MCF-7 and OE-33 cells grown in Matrigel reduced spheroid area. The results demonstrate that specific ablation of claudin expressing tumor cells is efficiently increased by activated C-CPE functionalized AuNPs using optical methods.
UR - http://www.scopus.com/inward/record.url?scp=85054593829&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-33392-0
DO - 10.1038/s41598-018-33392-0
M3 - Article
C2 - 30297847
AN - SCOPUS:85054593829
VL - 8
JO - Scientific reports
JF - Scientific reports
SN - 2045-2322
M1 - 14963
ER -