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Labeling Stem Cells with Ferumoxytol, an FDA-Approved Iron Oxide Nanoparticle
Published on: November 4, 2011
A degradable multi-metal-chelating stealth nanoplatform for dual ferroptosis/cuproptosis-enhanced
Yingying Wang1, Jianxiang Xu2, Wenhui Bai1
1Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Abstract:
Acute myeloid leukemia (AML) remains a challenging hematologic malignancy with limited treatment options and poor prognosis. Here, we report the development of a multifunctional, pH-responsive, and biodegradable nanoparticle system, Membrane/Cu-HMPB@DSF/RSL3, for synergistic AML therapy. Constructed upon the Prussian blue-based frameworks and cloaked with leukemia cell membranes, these nanoparticles preferentially accumulate in AML cells and release copper, iron, and manganese ions, along with disulfiram (DSF) and RSL3, under mildly acidic intracellular conditions. The released metal ions catalyze Fenton-like reactions, deplete intracellular glutathione (GSH), and induce ferroptosis and cuproptosis in cooperation with the loaded small-molecule drugs. Meanwhile, manganese ions activate the cGAS-STING pathway, triggering innate immune responses and promoting immune cell recruitment. Both in vitro and in vivo studies demonstrated robust anti-AML efficacy with minimal systemic toxicity. This work presents a modular and immunogenic nanoplatform that holds broad potential for AML treatment and beyond.
