Cuproptosis-mediated stemness inhibition by a self-assembled herbal nanoplatform overcomes chemoresistance in ovarian cancer.

Authors

Shanshan Liu, Yichun Huang, Fanchen Yan, Hailong Tian, Bowen Li, Yaying Zhang, Huili Zhu, Weihua Tong, Canhua Huang

Published in

Materials today. Bio. Volume 39. Pages 103440. Epub Jul 09, 2026.

Abstract

Ovarian cancer remains difficult to treat due to the persistence of chemoresistant cancer stem-like cells (CSCs), which are major drivers of tumor relapse. Herein, we engineered a hyaluronic acid-functionalized nanoplatform (HS-Cu@DOX) via the assembly of a shikonin-copper (SKN-Cu) coordination complex with hyaluronic acid, followed by electrostatic loading of doxorubicin (DOX), enabling tumor-targeted co-delivery of both therapeutic agents. This nanoplatform disrupts intracellular redox homeostasis to induce cuproptosis while concurrently suppressing CSC stemness through downregulation of key pluripotency-associated transcription factors (e.g., SOX2, OCT4, and NANOG). By depleting intracellular glutathione (GSH) and impairing antioxidant defenses, HS-Cu@DOX disrupts the oxidative stress resilience of CSCs, thereby restoring their sensitivity to DOX-induced apoptosis. Consequently, this strategy enhances DOX-mediated cytotoxicity and reduces systemic toxicity while maintaining potent antitumor efficacy. Collectively, our findings demonstrate that combining cuproptosis induction with CSC stemness suppression represents a promising strategy for overcoming chemoresistance, highlighting HS-Cu@DOX as a potential therapeutic candidate for recurrent ovarian cancer.

PMID:
42473540
Bibliographic data and abstract were imported from PubMed on 20 Jul 2026.

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