2. Academic Validation
  3. Lipid Droplet-Targeted Biomimetic Liposomes Potentiate Chemo-Ferroptosis Therapy in Leukemia

Lipid Droplet-Targeted Biomimetic Liposomes Potentiate Chemo-Ferroptosis Therapy in Leukemia

  • Adv Mater. 2026 Apr;38(20):e15716. doi: 10.1002/adma.202515716.
Xinyu Wang 1,  Cheng Liu 1,  Ran Ji 1,  Jiaxin Liu 1 2,  Yuyang Shao 1,  Shu Xia 1,  Jingyao Li 2,  Xiang Zhang 2,  Lingjie Luo 2,  Yanwei Wu 2,  Shao Q Yao 3,  Chao Fang 4,  Liang Chen 2,  Xiao Dong 1 2
Affiliations

Affiliations

  • 1 Shanghai 411 Hospital, China RongTong Medical Healthcare Group Co. Ltd./411 Hospital, Shanghai University, Shanghai, China.
  • 2 Institute of Artificial Intelligence and Biomanufacturing, Shanghai University, Shanghai, China.
  • 3 Department of Chemistry, National University of Singapore, Singapore, Singapore.
  • 4 Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 41814941 DOI: 10.1002/adma.202515716
Abstract

Chemotherapy remains the primary treatment modality for leukemia, yet relapse frequently occurs due to the persistence of chemoresistant leukemia cells (LCs) within the bone marrow (BM). Ferroptosis-based therapies provide a promising strategy for eliminating these resistant cells. Here, we demonstrate that cytarabine chemotherapy promotes lipid droplet (LD) accumulation in BM-resident LCs, thereby conferring resistance to Ferroptosis. Based on these findings, we developed a biomimetic Liposome (REM@HLipo) co-encapsulating RSL3 (a Ferroptosis inducer), elacytarabine (a cytarabine prodrug), and metformin (an LD disruptor) to enhance chemo-ferroptosis therapy against leukemia. Upon targeted delivery to BM-resident LCs, metformin disrupts LDs and increases the availability of polyunsaturated fatty acids (PUFAs) for oxidation, thereby sensitizing LCs to RSL3-induced Ferroptosis. This effect synergizes with cytarabine to exert potent cytotoxicity against BM-resident LCs in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) mouse models. Moreover, REM@HLipo significantly reduces leukemia stem cell populations in AML models. This study presents a novel chemo-ferroptosis therapeutic regimen for leukemia management.

Keywords

biomimetic liposome; ferroptosis; leukemia; lipid droplet; polyunsaturated fatty acid.

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