A novel targeted anticancer drug delivery strategy: Cnidium officinale polysaccharide conjugated with carboxymethyl-5-fluorouracil and folic acid for ovarian cancer therapy

Abstract

To mitigate adverse reactions induced by 5-fluorouracil (5-FU), Cnidium officinale fraction 2 (F2) polysaccharides served as the macromolecular carrier, facilitating its reaction with carboxymethyl-5-fluorouracil (C-5-FU) for producing F2-C-5-FU. Subsequently, this compound could react with folic acid (FA) through the ester bond, forming F2-C-5-FU-FA, as verified through NMR analysis. The in vitro anticancer efficacy of F2-C-5-FU-FA was evaluated using SKOV-3 cells that expressed folate receptor (FR) and FR-deficient A549 cells, showing greater cytotoxicity in the SKOV-3 cell line due to the FRs on the cell membrane. In vivo experiments were conducted on SKOV-3-bearing xenograft mice using an in vivo imaging system (IVIS). Animals injected with F2-C-5-FU-FA exhibited significantly stronger targeting of tumor tissue compared to those injected with F2-C-5-FU. These findings highlighted enhanced drug delivery and accumulation in targeted tumor regions facilitated by folate-targeted conjugates. Moreover, F2-C-5FU-FA showed reduced cardiac toxicity in mice and minimal spleen accumulation, indicating a negligible effect on the immune system. Overall, this study introduced a novel strategy for achieving highly efficient anticancer drug delivery into tumor cells that express FR.

Keywords: 5-fluorouracil; Anticancer; Drug deliver; Folic acid; Polysaccharide.