Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
School of Life Science and Biopharmaceutics Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
Adv Healthc Mater. 2024 Jul;13(18):e2304485. doi: 10.1002/adhm.202304485. Epub 2024 Apr 22.
Ferroptosis is identified as a potential target for anticancer therapy. However, most conventional ferroptosis inducers not only fail to trigger intracellular lipid peroxidation storm, but are also prone to cause ferroptosis-related toxicity through off-target destruction of intracellular antioxidant defense systems. Therefore, a potent and highly tumor-specific ferroptosis induction modality is desired. Herein, a self-cooperative nanomedicine for imaging-guided photothermal ferrotherapy, which is fabricated based on molecular nanoassembly (NA) of DiR (a photothermal probe) and ferrocene (Fc, a reactant of the Fenton reaction), is elaborately exploited. DiR-elicited hyperthermia induces both photothermal therapy (PTT) and a significant acceleration of the kinetics of the Fc-involved Fenton reaction, collaboratively causing a lipid peroxidation storm in tumor cells. In turn, plenty of lipid peroxides boost PTT through the downregulation of heat shock protein 90. As expected, such a self-cooperative NA demonstrates synergetic tumor eradication in the 4T1 breast tumor-bearing mice xenograft model. This study offers a novel nanotherapeutic paradigm for precise multimodal cancer therapy.
铁死亡被认为是癌症治疗的一个潜在靶点。然而，大多数传统的铁死亡诱导剂不仅不能引发细胞内脂质过氧化爆发，而且还容易通过靶向破坏细胞内抗氧化防御系统而引起铁死亡相关毒性。因此，需要一种有效且高度肿瘤特异性的铁死亡诱导方式。在这里，我们精心开发了一种基于近红外染料（DiR，一种光热探针）和二茂铁（Fc，芬顿反应的反应物）的分子纳米组装（NA）构建的用于成像引导光热铁疗法的自协同纳米药物。DiR 诱导的热疗既诱导光热疗法（PTT），又显著加速 Fc 参与的芬顿反应的动力学，协同导致肿瘤细胞内的脂质过氧化爆发。反过来，大量的脂质过氧化物通过下调热休克蛋白 90 来增强 PTT。正如预期的那样，这种自协同 NA 在 4T1 乳腺癌荷瘤小鼠异种移植模型中表现出协同的肿瘤消除作用。本研究为精确的多模态癌症治疗提供了一种新的纳米治疗范例。
