Construction of folic acid modified fluoro-liposomes for oral delivery of erastin to achieve targeted anti-tumor therapy.

Abstract

Erastin, as an effective ferroptosis inducer, has received extensive attention in anti-tumor research. To develop an oral nanocarrier for high efficient loading hydrophobic erastin, here we prepared a fluoro-liposome (FA-3 F-LS) by the self-assembly of the folic acid modified fluorinated amphiphiles-FA-3 F conjugates. The hydrophobic component of three perfluorooctyl chains endows the FA-3 F-LSs with high stability to resist the harsh gastrointestinal tract condition. Folic acids conjugated on the surface of FA-3 F-LSs ensure the better tumor targeting and higher oral bioavailability (32.1%) of erastin-loaded FA-3 F-LSs (erastin@FA-3 F-LSs) than free erastin (8.98%). As targeted anti-tumor nanomedicines, erastin@FA-3 F-LSs effectively inhibited the tumor cell proliferation in vitro by inducing ferroptosis through enhancing the glutathione (GSH) depletion, lipid peroxidation and generation of reactive oxygen species. In vivo studies demonstrated that FA-3 F-LSs displayed excellent application potential as a tumor-targeted oral drug delivery nanocarrier to depress the tumor growth with the loaded chemotherapeutic agents.