化学动力学疗法（CDT）因其微创性、减少对健康组织的损害以及潜在的副作用减轻而在治疗多种恶性肿瘤方面引起了广泛关注。然而，其在胶质母细胞瘤 (GBM) 中的应用受到 CDT 药物穿越血脑屏障 (BBB) 能力减弱、肿瘤靶向效率不足以及肿瘤微环境 (TME) 内 H2O2 可用性有限的阻碍。为了应对这些挑战，我们设计了一种基于四面体框架核酸（tFNA）的新型 CDT 试剂（Fe@tFNAs-ANG-3AT）。 Fe@tFNAs-ANG-3AT 是通过将铁离子 (Fe3+) 锚定到双附件修饰的 tFNA 上而构建的。具体来说，Angiopep-2（ANG，一种穿透肽）这一附属物可促进 Fe@tFNAs-ANG-3AT 穿透 BBB 并选择性靶向肿瘤细胞。同时，第二个附属物 3-氨基-1,2,4-三唑（3AT，一种 H2O2 酶抑制剂）可增加有效 CDT 治疗所需的 H2O2 水平。肿瘤细胞内化后，Fe@tFNAs-ANG-3AT 中负载的 Fe3 被 TME 中过表达的谷胱甘肽 (GSH) 还原为 Fe2，催化细胞毒性羟基自由基 (·OH) 的产生，并通过升高的氧化诱导肿瘤细胞死亡肿瘤细胞内的应激水平。预计 Fe@tFNAs-ANG-3AT 有望成为 GBM 的变革性治疗策略。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Chemodynamic therapy (CDT) has garnered significant attention for treating diverse malignant tumours due to its minimally invasive nature, reduced damage to healthy tissues, and potential mitigation of side effects. However, its application in glioblastoma (GBM) is hindered by the diminished capacity of CDT agents to traverse the blood-brain barrier (BBB), inadequate tumour targeting efficiency, and restricted availability of H2O2 within the tumour microenvironment (TME). To address these challenges, we devised a novel CDT agent (Fe@tFNAs-ANG-3AT) based on a tetrahedral framework nucleic acids (tFNAs). Fe@tFNAs-ANG-3AT was constructed by anchoring iron ions (Fe3+) onto the dual appendages-modified tFNAs. Specifically, one appendage, Angiopep-2 (ANG, a penetrating peptide), facilitates Fe@tFNAs-ANG-3AT penetration across the BBB and selective targeting of tumour cells. Simultaneously, the second appendage, 3-Amino-1,2,4-triazole (3AT, a H2O2 enzyme inhibitor), augments the H2O2 levels required for effective CDT treatment. Upon tumour cell internalization, the loaded Fe3+ in Fe@tFNAs-ANG-3AT is reduced to Fe2+ by the overexpressed glutathione (GSH) in the TME, catalysing the generation of cytotoxic hydroxyl radicals (·OH) and inducing tumour cell death via elevated oxidative stress levels within tumour cells. It is anticipated that Fe@tFNAs-ANG-3AT holds promise as a transformative treatment strategy for GBM.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.