Non-small cell lung cancer (NSCLC) is a type of cancer dominated by metastasis-induced death. The transcription factor BTB and CNC homology 1 (Bach1) regulates almost all metastasis steps by activating the transcription of critical metastatic genes. It is urgent to engineer a nanodrug enabling regulation of Bach1 against tumor metastasis. Herein, a minimalist nanodrug integrating chemodynamic therapy (CDT) and Bach1 degradation was reported to prevent metastasis of NSCLC. The nanodrug was achieved by self-assembly of ferrocene (Fc) and Tin protoporphyrin IX (TinPPIX). In our nanodrug, Fc not only triggers the production of highly cytotoxic ∙OH for tumor ablation via Fenton reaction, but also induces heme release from heme-containing proteins to stimulate Bach 1 degradation. Moreover, TinPPIX further augments the free heme level along with amplifies the CDT efficacy by disabling heme oxygenase-1 (HO-1)-mediated heme conversion into antioxidative bilirubin. The results showed that, compared with control group, TinPPIX/Fc nanodrug caused a four-fold increase in heme level, which triggered remarkable Bach1 degradation in Fbxo22-mediated manner and successfully inhibited Bach1-dominated metastasis. Therefore, this nanodrug could powerfully impeded NSCLC progression and metastasis, offering an innovative heme-regulatable chemodynamic therapeutic approach for lung cancer with strong metastasis capability.

非小细胞肺癌（NSCLC）是一种以转移引起的死亡为主的癌症。转录因子 BTB 和 CNC 同源 1 (Bach1) 通过激活关键转移基因的转录来调节几乎所有转移步骤。迫切需要设计一种能够调节 Bach1 以对抗肿瘤转移的纳米药物。据报道，一种结合化学动力学疗法（CDT）和 Bach1 降解的极简纳米药物可预防 NSCLC 转移。该纳米药物是通过二茂铁（Fc）和锡原卟啉IX（TinPPIX）的自组装实现的。在我们的纳米药物中，Fc 不仅通过 Fenton 反应触发产生高细胞毒性的 ∙OH 用于肿瘤消融，而且还诱导含血红素的蛋白质释放血红素以刺激 Bach 1 降解。此外，TinPPIX 通过阻止血红素加氧酶-1 (HO-1) 介导的血红素转化为抗氧化胆红素，进一步提高游离血红素水平并增强 CDT 功效。结果显示，与对照组相比，TinPPIX/Fc纳米药物引起血红素水平增加四倍，从而以Fbxo22介导的方式引发显着的Bach1降解，并成功抑制Bach1主导的转移。因此，这种纳米药物可以有力地阻止NSCLC的进展和转移，为具有强转移能力的肺癌提供一种创新的血红素调节化学动力学治疗方法。