ArticleJournal of hematology & oncology2021
A lysosome-targeted dextran-doxorubicin nanodrug overcomes doxorubicin-induced chemoresistance of myeloid leukemia.
Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 24 citations in OpenAlex.
- PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.Molecular medicine reports · 2026Article
- CLN7 suppression induces apoptosis via mTOR-regulated and chaperone-mediated autophagy in myeloid leukemia cells.Cell death & disease · 2026Article
- The Role of Lipid Rafts in the Mitogen-Activated Protein Kinase Signaling in Cancer.Current medicinal chemistry · 2026Review
- Emerging magic bullet: subcellular organelle-targeted cancer therapy.Medical review (2021) · 2025Review
- Article
- Inhibition of CRM1 reverses hypoxia-driven chemoresistance in acute myeloid leukemia via overcoming HIF-1α-mediated lysosomal sequestration.Frontiers in immunology · 2025Article
- Targeting TNF/IL-17/MAPK pathway in hHaematologica · 2024Article
- Tumor metabolic crosstalk and immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Hypoxia-ameliorated photothermal manganese dioxide nanoplatform for reversing doxorubicin resistance.Frontiers in pharmacology · 2023Article
- Clinical Efficacy of Medical Dextrose Tincture Liquid in the Treatment of Facial Photoaging.Dermatology practical & conceptual · 2023Article
- A tumor microenvironment-responsive micelle co-delivered radiosensitizer Dbait and doxorubicin for the collaborative chemo-radiotherapy of glioblastoma.Drug delivery · 2022Article
- Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer.Journal of nanobiotechnology · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
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Abstract
The hypoxic microenvironment is presumed to be a sanctuary for myeloid leukemia cells that causes relapse following chemotherapy, but the underlying mechanism remains elusive. Using a zebrafish xenograft model, we observed that the hypoxic hematopoietic tissue preserved most of the chemoresistant leukemic cells following the doxorubicin (Dox) treatment. And hypoxia upregulated TFEB, a master regulator of lysosomal biogenesis, and increased lysosomes in leukemic cells. Specimens from relapsed myeloid leukemia patients also harbored excessive lysosomes, which trapped Dox and prevented drug nuclear influx leading to leukemia chemoresistance. Pharmaceutical inhibition of lysosomes enhanced Dox-induced cytotoxicity against leukemic cells under hypoxia circumstance. To overcome lysosome associated chemoresistance, we developed a pH-sensitive dextran-doxorubicin nanomedicine (Dex-Dox) that efficiently released Dox from lysosomes and increased drug nuclear influx. More importantly, Dex-Dox treatment significantly improved the chemotherapy outcome in the zebrafish xenografts transplanted with cultured leukemic cells or relapsed patient specimens. Overall, we developed a novel lysosome targeting nanomedicine that is promising to overcome the myeloid leukemia chemoresistance.
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