自组装草药纳米平台对Curoptosis介导的干性抑制克服了卵巢癌症的化疗耐药性
Cuproptosis-mediated stemness inhibition by a self-assembled herbal nanoplatform overcomes chemoresistance in ovarian cancer.
摘要(中文译文)
卵巢癌因化疗耐药的癌干样细胞（CSCs）持续存在而仍然难以治疗，这类细胞是肿瘤复发的主要驱动因素。在此，我们通过将紫草素-铜（SKN-Cu）配位复合物与透明质酸组装，随后静电负载多柔比星（DOX），构建了一种透明质酸功能化纳米平台（HS-Cu@DOX），实现了两种治疗药物的肿瘤靶向共递送。该纳米平台破坏细胞内氧化还原稳态以诱导铜死亡，同时通过下调关键多能性相关转录因子（如SOX2、OCT4和NANOG）抑制CSC干性。通过耗竭细胞内谷胱甘肽（GSH）并削弱抗氧化防御，HS-Cu@DOX破坏了CSCs的氧化应激耐受性，从而恢复其对DOX诱导凋亡的敏感性。因此，该策略增强了DOX介导的细胞毒性并降低了全身毒性，同时保持了强效的抗肿瘤疗效。总体而言，我们的研究结果表明，将铜死亡诱导与CSC干性抑制相结合是克服化疗耐药的一种有前景的策略，凸显了HS-Cu@DOX作为复发性卵巢癌潜在治疗候选药物的价值。
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.
如何引用
AMA
Shanshan Liu, Yichun Huang, Fanchen Yan, Hailong Tian, Bowen Li, Yaying Zhang, et al. Cuproptosis-mediated stemness inhibition by a self-assembled herbal nanoplatform overcomes chemoresistance in ovarian cancer.. Materials today. Bio. 2026; doi:10.1016/j.mtbio.2026.103440.
APA
Shanshan Liu, Yichun Huang, Fanchen Yan, Hailong Tian, Bowen Li, Yaying Zhang, et al (2026). Cuproptosis-mediated stemness inhibition by a self-assembled herbal nanoplatform overcomes chemoresistance in ovarian cancer.. Materials today. Bio. https://doi.org/10.1016/j.mtbio.2026.103440
GB/T 7714
Shanshan Liu, Yichun Huang, Fanchen Yan, Hailong Tian, Bowen Li, Yaying Zhang, et al. Cuproptosis-mediated stemness inhibition by a self-assembled herbal nanoplatform overcomes chemoresistance in ovarian cancer.[J]. Materials today. Bio, 2026 doi:10.1016/j.mtbio.2026.103440.
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