题目：

A Two-Pronged Nanostrategy of Iron Metabolism Disruption to Synergize Tumor Therapy by Triggering the Paraptosis–Apoptosis Hybrid Pathway

作者：

Huali Lei¹, Guanghui Hou¹*, Lin Liu², Zifan Pei¹, Youdong Chen¹, Yujie Lu¹, Nalin Yang¹, Shumin Sun¹, and Liang Cheng¹*

单位：

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

²Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

摘要：

Iron metabolism has emerged as a promising target for cancer therapy; however, the innate metabolic compensatory capacity of cancer cells significantly limits the effectiveness of iron metabolism therapy. Herein, bioactive gallium sulfide nanodots (GaS_x), with dual functions of "reprogramming" and "interfering" iron metabolic pathways, were successfully developed for tumor iron metabolism therapy. The constructed GaS_x nanodots ingeniously harness hydrogen sulfide (H₂S) gas, which is released in response to the tumor microenvironment, to reprogram the inherent transferrin receptor 1 (TfR1)-ferroportin 1 (FPN1) iron metabolism axis in cancer cells. Concurrently, the gallium ions (Ga³⁺) derived from GaS_x act as a biochemical "Trojan horse", mimicking the role of iron and displacing it from essential biomolecular binding sites, thereby influencing the fate of cancer cells. By leveraging the dual mechanisms of Ga³⁺-mediated iron disruption and H₂S-facilitated reprogramming of iron metabolic pathways, GaS_x prompted the initiation of a paraptosis–apoptosis hybrid pathway in cancer cells, leading to marked suppression of tumor proliferation. Importantly, the dysregulation of iron metabolism induced by GaS_x notably increased tumor cell susceptibility to both chemotherapy and immune checkpoint blockade (ICB) therapy. This study underscores the therapeutic promise of gas-based interventions and metal ion interference strategies for the tumor metabolism treatment.

影响因子：

15.8

分区情况：

一区

链接：

https://doi.org/10.1021/acsnano.4c06199

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