Abstract
Abstract In this study we identified the proton-coupled folate transporter (PCFT) as a route for targeted delivery of drugs to glioma cells. Using the techniques of confocal imaging, western blotting, and siRNA knockdown against the PCFT (encoded by the SLC46A1 gene), we demonstrated that Gl261 glioma cells, but not primary cultured astrocytes, express the PCFT, which provides selective internalization of folic acid (FA)-conjugated cytochrome c-containing nanoparticles (FA-Cyt c NPs), followed by glioma cell death. FA-Cyt c NPs, used at a concentration of 100 µg/ml, had no cytotoxic effects in astrocytes but caused 40% death in GL261 cells. Whole-cell patch clamp recording revealed FA-induced membrane currents, with maximum activity at pH 6.0, which is specific for the PCFT. Currents were reduced by siRNA PCFT knockdown in a similar manner as by application of FA-Cyt c NPs, indicating that the PCFT is a major carrier of FA and a route for internalization of FA-conjugated NPs in GL261 cells. We conclude that the PCFT provides a mechanism for targeted delivery of FA-conjugated nanodrugs to glioma cells with high specificity for GL261 cells, effectively causing apoptosis in these cells, and provides a starting point for the development of efficient methods for treating gliomas. The research was supported by NIH grants SC2GM102040, SC2GM095410, G12MD007583, R25GM110513, and US Department of Education Grant P031S130068. Citation Format: Yuriy Kucheryavykh, Jescelica Ortiz-Rivera, Michael Inyushin, Luis Cubano, Moraima Morales-Cruz, Alejandra Cruz-Montañez, Kai Griebenow, Lilia Kucheryavykh. Targeted delivery of nanoparticulate cytochrome c into GL261 glioma cells through the proton-coupled folate transporter [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2179. doi:10.1158/1538-7445.AM2017-2179
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
