Abstract：
The unique \"Iron Addiction\" feature of cancer stem cells (CSCs) with tumorigenicity and plasticity generally contributes to the tumor recurrence and metastasis after a lumpectomy. Herein, a novel \"Ferroptosis Amplification\" strategy is developed based on integrating gallic acid-modified FeOOH (GFP) and gallocyanine into Pluronic F-127 (F127) and carboxylated chitosan (CC)-based hydrogel for CSCs eradication. This \"Ferroptosis Amplifier\" hydrogel is thermally sensitive and achieves rapid gelation at the postsurgical wound in a breast tumor model. Specifically, gallocyanine, as the Dickkopf-1 (DKK1) inhibitor, can decrease the expression of SLC7A11 and GPX4 and synergistically induce ferroptosis of CSCs with GFP. Encouragingly, it is found that this combination suppresses the migratory and invasive capability of cancer cells via the downregulation of matrix metalloproteinase 7 (MMP7). The in vivo results further confirm that this \"Ferroptosis Amplification\" strategy is efficient in preventing tumor relapse and lung metastasis, manifesting an effective and promising postsurgical treatment for breast cancer.
摘要：
具有致瘤性和可塑性的癌症干细胞（CSC）的独特“铁成瘾”特征通常有助于肿瘤切除术后的肿瘤复发和转移。在这里，基于将没食子酸修饰的FeOOH（GFP）和gallocyanine整合到PluronicF-127（F127）和羧化壳聚糖（CC）基水凝胶中，以根除CSC，开发了一种新型的“Ferroptosis扩增”策略。这种“FerroptosisAmplifier”水凝胶对热敏感，并在乳腺肿瘤模型的术后伤口中实现快速凝胶化。具体来说,gallocyanine,作为Dickkopf-1（DKK1）抑制剂，可以降低SLC7A11和GPX4的表达，并与GFP协同诱导CSCs的铁凋亡。令人鼓舞的是，发现这种组合通过下调基质金属蛋白酶7（MMP7）抑制癌细胞的迁移和侵袭能力。体内研究结果进一步证实，这种“Ferroptosis扩增”策略在预防肿瘤复发和肺转移方面是有效的，显示出有效和有希望的乳腺癌术后治疗。
