Erianin-Loaded AS1411 Aptamer–Albumin Nanoparticles Enhance Antiesophageal Cancer Efficacy by Inducing Ferroptosis

Esophageal cancer (EC) has a high incidence and mortality worldwide with a poor prognosis, and using targeted nanopreparations to treat EC is a promising therapeutic strategy. In this study, a drug delivery carrier AS1411-bovine serum albumin (BSA) that targets EC cells was prepared by conjugation technology. The carrier could be specifically internalized by KYSE520 cells with high expression of nucleolin and achieved targeted accumulation in tumor tissues of xenograft models. The AS1411-BSA@ERN nanoparticles, which were prepared by encapsulating erianin (ERN) with AS1411-BSA, exhibited a suitable particle size and good sustained-release characteristics. A series of experimental results, involving the CCK-8 assay and live/dead cell assay, showed that AS1411-BSA@ERN effectively inhibited the proliferation of EC cells. Analysis of ferroptosis-related indicators revealed that AS1411-BSA@ERN depleted glutathione (GSH) and caused an increase in Fe²⁺, reactive oxygen species (ROS), and lipid peroxidation, leading to ferroptosis in EC cells. In KYSE520 and EC109 xenograft models, AS1411-BSA@ERN nanoparticles significantly inhibited tumor growth without obvious side effects. Overall, the high targeting ability of AS1411 and the multifunctionality of albumin could enhance ERN efficacy against EC, inhibit the proliferation of EC cells, and induce ferroptosis. AS1411-BSA@ERN nanoparticles may be a targeted ferroptosis inducer, providing a potential strategy for targeted treatment against EC.