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.
Highlights
We demonstrated that C-terminal of Clostridium perfringens enterotoxin (C-Clostridium perfringens enterotoxin (CPE))-AuNPs can be used to and efficiently ablate different human cell lines expressing CLDN-3, -4, and -7 by gold-nanoparticle-mediated laser perforation (GNOME-LP) technique [43,44]
This study aimed to evaluate the elimination of stably transfected canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) tumor cell lines using C-CPE-AuNPs complex and GNOME-LP, and characterize, if the red fluorescent cell lines emission interferes with conventional laser ablation and optimized the required parameters in vitro
Gene expression level of CLDN-3, -4, and -7 in transfected cell lines were examined by quantitative real-time RT-PCR and compared to the native cell lines
Summary
Prostate cancer is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death among men in 2020 [1,2]. The disease is at present incurable once it has metastasized, as metastases are highly resistant to current conventional therapies. Aside from humans, dogs are known to naturally develop prostate cancer [3]. In both species, adenocarcinomas of the prostate represent a locally invasive disease [4]
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