2. Academic Validation
  3. A Ferroptosis-Inducing and Leukemic Cell-Targeting Drug Nanocarrier Formed by Redox-Responsive Cysteine Polymer for Acute Myeloid Leukemia Therapy

A Ferroptosis-Inducing and Leukemic Cell-Targeting Drug Nanocarrier Formed by Redox-Responsive Cysteine Polymer for Acute Myeloid Leukemia Therapy

  • ACS Nano. 2023 Feb 8. doi: 10.1021/acsnano.2c06313.
Yanhui Yu 1 2 3 4,  Yabin Meng 5,  Xi Xu 2 3 6,  Tong Tong 5,  Chong He 2 3 6,  Liying Wang 5,  Kaitao Wang 3 6,  Minyi Zhao 7,  Xinru You 5,  Wenwen Zhang 3 6,  Linjia Jiang 2,  Jun Wu 2 8 9,  Meng Zhao 2 3 6
Affiliations

Affiliations

  • 1 Department of Hematology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi Medical College, Changzhi, Shanxi 046000, China.
  • 2 RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510410, China.
  • 3 Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
  • 4 Department of Hematology, People's Hospital of Zhangzi, Changzhi, Shanxi 046000,China.
  • 5 School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
  • 6 Key Laboratory of Stem Cells and Tissue Engineering (Ministry of Education), Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
  • 7 Department of Hematology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518000, China.
  • 8 Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China.
  • 9 Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou, 511400, Guangdong, China.
PMID: 36752654 DOI: 10.1021/acsnano.2c06313
Abstract

Ferroptosis is an alternative strategy to overcome chemoresistance, but effective therapeutic approaches to induce Ferroptosis for acute myeloid leukemia (AML) treatment are limited. Here, we developed glutathione (GSH)-responsive cysteine polymer-based ferroptosis-inducing nanomedicine (GCFN) as an efficient Ferroptosis inducer and chemotherapeutic drug nanocarrier for AML treatment. GCFN depleted intracellular GSH and inhibited Glutathione Peroxidase 4, a GSH-dependent hydroperoxidase, to cause lipid peroxidation and Ferroptosis in AML cells. Furthermore, GCFN-loaded paclitaxel (PTX@GCFN) targeted AML cells and spared normal hematopoietic cells to limit the myeloablation side effects caused by paclitaxel. PTX@GCFN treatment extended the survival of AML mice by specifically releasing paclitaxel and simultaneously inducing Ferroptosis in AML cells with restricted myeloablation and tissue damage side effects. Overall, the dual-functional GCFN acts as an effective Ferroptosis inducer and a chemotherapeutic drug carrier for AML treatment.

Keywords

chemotherapy; drug targeting; ferroptosis; leukemia; myeloablation.

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