A folate-appended cyclodextrin carrier targets ovarian cancer cells expressing the proton-coupled folate transporter

Cancer Science
Shinichi SaitoAkihiro Nawa

Abstract

Folate receptor alpha (FRα) is overexpressed in > 80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as first-line chemotherapeutic agent in combination with platinum-based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor-EL, a traditional formulation vehicle that causes significant side effects including neutropenia. Recently, folate-appended β-CyD (Fol-c1 -β-CyD) was developed as an FRα-targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol-c1 -β-CyD (PTX/Fol-c1 -β-CyD) in EOC-derived cell lines. We found that PTX/Fol-c1 -β-CyD killed not only FRα-expressing cells, but also FRα-negative cells. In the FRα-negative A2780 cells, knockdown of proton-coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol-c1 -β-CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or PCFT decreased the cytotoxicity of PTX/Fol-c1 -β-CyD in FRα-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c1 -β-CyD in A2780 cells...Continue Reading

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Citations

Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jun XueHui Zhou

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