A DNA Nanomachine Modulates the Stemness-Associated Signaling Pathways for Overcoming Chemoresistance by Temporally Programming Drug Release.

ABSTRACT: Chemoresistance is a primary cause of cancer treatment failure, due to the lack of specific regulatory strategies arising from unclear mechanisms. Here, we uncover the pivotal role of the PRMT1/SOX2 axis in regulating cancer stemness, a key factor contributing to cancer chemoresistance. In light of this, we construct a DNA nanomachine (DNM) to overcome chemoresistance by reversing cancer stemness. This DNM is constructed using a programmable DNA origami framework, incorporating CD44-targeting aptamers and glutathione (GSH)-responsive stemness inhibitors (DCLX069) as functional components. The DNM exhibits a specific affinity toward CD44-overexpressing tumor cells, enabling the effective delivery of the loaded cisplatin (CDDP) to the tumor cells. Upon entering the tumor cells, DCLX069 is ra

SUBMITTER: Chen J 

PROVIDER: S-EPMC12687658 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature