Scheme 1.

Schematic showing mEVs-mediated FDX oral delivery for cancer therapy. The effective anticancer efficacy of orally administered FDX, facilitated by mEVs, is primarily attributed to a two-stage process. Initially, the interaction between the IgG present on the mEVs and the FcRn in the intestinal epithelium induces transcytosis of FDX@mEVs, thereby enhancing the limited bioavailability of FDX and elevating its systemic exposure. Subsequently, the enhanced bioavailability of FDX, mediated by mEVs, contributes to its accumulation in tumor sites. This phenomenon results in increased antitumor effects of FDX@mEVs.