ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
A Metabolic Reprogramming Amino Acid Polymer as an Immunosurveillance Activator and Leukemia Targeting Drug Carrier for T-Cell Acute Lymphoblastic Leukemia.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
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- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- Amino acid metabolic reprogramming drives pathogenesis and therapy in hematologic malignancies.Discover oncology · 2025Review
- Green PEGylated-Sily@ZnFe2O4 nanocomposites for amelioration of ROS and DNA damage in rat liver.Scientific reports · 2025Article
- Amino acids shape the metabolic and immunologic landscape in the tumor immune microenvironment: from molecular mechanisms to therapeutic strategies.Cancer biology & medicine · 2025Review
- Advances in nanoparticle-mediated cancer therapeutics: Current research and future perspectives.Cancer pathogenesis and therapy · 2025Review
- Nanodrug Delivery Systems for Acute Lymphoblastic Leukemia Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
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- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.Theranostics · 2025Review
- CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies.Frontiers in immunology · 2025Review
- Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance.Pharmaceutics · 2024Review
- Nanotechnology Advances in the Detection and Treatment of Lymphoid Malignancies.International journal of molecular sciences · 2024Review
- Targeted therapy for leukemia based on nanomaterials.Heliyon · 2024Review
- GSH-responsive degradable nanodrug for glucose metabolism intervention and induction of ferroptosis to enhance magnetothermal anti-tumor therapy.Journal of nanobiotechnology · 2024Article
- Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer.Signal transduction and targeted therapy · 2024Article
- Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Article
- Causal pathways in lymphoid leukemia: the gut microbiota, immune cells, and serum metabolites.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Compromised immunosurveillance leads to chemotherapy resistance and disease relapse of hematological malignancies. Amino acid metabolism regulates immune responses and cancer; however, a druggable amino acid metabolite to enhance antitumor immunosurveillance and improve leukemia targeting-therapy efficacy remains unexplored. Here, an L-phenylalanine polymer, Metabolic Reprogramming Immunosurveillance Activation Nanomedicine (MRIAN), is invented to effectively target bone marrow (BM) and activate the immune surveillance in T-cell acute lymphoblastic leukemia (T-ALL) by inhibiting myeloid-derived suppressor cells (MDSCs) in T-ALL murine model. Stable-isotope tracer and in vivo drug distribution experiments show that T-ALL cells and MDSCs have enhanced cellular uptake of L-phenylalanine and MRIANs than normal hematopoietic cells and progenitors. Therefore, MRIAN assembled Doxorubicin (MRIAN-Dox) specifically targets T-ALL cells and MDSCs but spare normal hematopoietic cells and hematopoietic stem and progenitor cells with enhanced leukemic elimination efficiency. Consequently, MRIAN-Dox has reduced cardiotoxicity and myeloablation side effects in treating T-ALL mice. Mechanistically, MRIAN degrades into L-phenylalanine, which inhibits PKM2 activity and reduces ROS levels in MDSCs to disturb their immunosuppressive function and increase their differentiation toward normal myeloid cells. Overall, a novel amino acid metabolite nanomedicine is invented to treat T-ALL through the combination of leukemic cell targeting and immunosurveillance stimulation.
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Registered trials
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