2. Academic Validation
  3. Engineered cell membrane vesicles loaded with lysosomophilic drug for acute myeloid leukemia therapy via organ-cell-organelle cascade-targeting

Engineered cell membrane vesicles loaded with lysosomophilic drug for acute myeloid leukemia therapy via organ-cell-organelle cascade-targeting

  • Biomaterials. 2025 Jun:317:123091. doi: 10.1016/j.biomaterials.2025.123091.
Fangfang Jin 1,  Xingyu Wei 1,  Yongcan Liu 1,  Lisha Tang 1,  Jun Ren 1,  Jing Yang 1,  Can Lin 1,  Jiayuan Hu 1,  Minghui Sun 1,  Genyou Li 1,  Zihao Yuan 1,  Wen Zhao 1,  Xiaozhong Wang 2,  Zesong Yang 3,  Ling Zhang 4
Affiliations

Affiliations

  • 1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 3 Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 4 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China. Electronic address: lingzhang@cqmu.edu.cn.
PMID: 39778270 DOI: 10.1016/j.biomaterials.2025.123091
Abstract

Acute myeloid leukemia (AML) presents significant treatment challenges due to the severe toxicities and limited efficacy of conventional therapies, highlighting the urgency for innovative approaches. Organelle-targeting therapies offer a promising avenue to enhance therapeutic outcomes while minimizing adverse effects. Herein, inspired that primary AML cells are enriched with lysosomes and sensitive to lysosomophilic drugs (e.g., LLOMe), we developed a smart nanodrug (Cas-CMV@LM) including the engineered cell membrane vesicles (CMVs) nanocarrier and the encapsulated drug cargo LLOMe (LM). Briefly, the nanodrug with organ-cell-organelle cascade-targeting function could firstly home to the bone marrow guided by CMVs derived from CXCR4-overexpressing bone marrow mesenchymal stem cells (BMSC), subsequently target leukemia cells via CD33 and CD123 Aptamers anchored on the vesicles, eventually precisely attack the lysosomes of leukemia cells. Consequently, Cas-CMV@LM specifically inhibited leukemia cell proliferation and triggered Necroptosis in vitro. Importantly, the cascade-targeting nanodrug displayed high biosafety and significantly impeded leukemia progression in AML patient-derived xenograft (PDX) model. Collectively, this study provides a paradigm for precision leukemia treatment from the perspective of targeting organelle-lysosome.

Keywords

Acute myeloid leukemia; Cell membrane vesicles; LLOMe; Lysosomes; Organelle-targeting.

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