Dual-Multivalent Aptamer-Based Drug Delivery Platform for Targeted SRC Silencing to Enhance Doxorubicin Sensitivity in Endometrial Cancer

Endometrial cancer poses a significant threat to women's health. Doxorubicin is commonly used in chemotherapy for advanced and recurrent cases; however, low sensitivity frequently limits its effectiveness. In this study, we verified that SRC modulates the sensitivity of endometrial cancer to chemotherapy of doxorubicin and developed a targeted silencing drug delivery platform that employs rolling circle amplification and dual-multivalent aptamers to precisely deliver therapeutics directly to tumor cells. This platform enhanced endometrial cancer cell sensitivity to doxorubicin by modulating drug responsiveness at the genetic level. Our results suggest that this approach may improve cancer cell susceptibility to ferroptosis. The efficacy and safety of this platform were validated in both cellular and animal models. This study provides a new solution for realizing the precision treatment of endometrial cancer and lays a theoretical foundation for exploring the mechanism of endometrial cancer.