Evidence map›Paper›PMID 40148810›Full record

ArticleJournal of nanobiotechnology2025

5-FU@HFn combined with decitabine induces pyroptosis and enhances antitumor immunotherapy for chronic myeloid leukemia.

Zuowei Yuan, Guoyun Jiang, Ying Yuan, Qian Liang, Yaxin Hou, Wenyao Zhang, Lujia Tang, Kelong Fan, Wenli Feng

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Zuowei Yuan *Department of Clinical Hematology, School of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China.
Guoyun Jiang *Department of Clinical Hematology, School of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China.
Ying Yuan *Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Qian LiangNanozyme Laboratory in Zhongyuan, Henan Academy of Innovations in Medical Science, Zhengzhou, Henan, 451163, China.
Yaxin HouKey Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS Engineering Laboratory for Nanozyme, Chinese Academy of Sciences, Beijing, 100101, China.
Wenyao ZhangDepartment of Clinical Hematology, School of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China.
Lujia TangDepartment of Clinical Hematology, School of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China.
Kelong FanNanozyme Laboratory in Zhongyuan, Henan Academy of Innovations in Medical Science, Zhengzhou, Henan, 451163, China. fankelong@ibp.ac.cn.
Wenli FengDepartment of Clinical Hematology, School of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China. fengwl@cqmu.edu.cn.

Funding

National Natural Science Foundation of China 32201167National Natural Science Foundation of China 81772255Natural Science Foundation of Shandong Province ZR2023QH062
6 · The paper itself

Abstract

backgroundTyrosine kinase inhibitors (TKIs) constitute the primary treatment for chronic myeloid leukemia (CML). However, resistance to TKIs often leads to treatment failure. Pyroptosis, a form of programmed cell death, has emerged as a promising strategy in cancer therapy due to its ability to eliminate tumor cells while stimulating antitumor immunity. Low-dose decitabine (DAC) has been shown to reverse methylation-induced silencing of the pyroptosis-related gene gasdermin E (GSDME) in some tumor cells, offering a potential new therapeutic option for CML. Herein, we propose a combination therapy using 5-fluorouracil (5-FU), a broad-spectrum chemotherapeutic agent, and low-dose DAC to induce pyroptosis in CML cells via the caspase-3/GSDME pathway. However, the nonspecific targeting of 5-FU diminishes its pyroptosis efficacy and causes off-target toxicity, highlighting the need for a targeted drug delivery system.

resultsIn this study, we developed 5-FU@HFn nanoparticles (NPs) by loading 5-FU into the recombinant human heavy chain ferritin (HFn) nanocage through a high-temperature via the drug channels on the protein cage. The loading efficiency was approximately 50.62 ± 1.17 µg of 5-FU per mg of HFn. 5-FU@HFn NPs selectively targeted CML cells through CD71-mediated uptake, significantly enhancing the therapeutic effects of 5-FU. When combined with DAC, 5-FU@HFn NPs effectively activated pyroptosis via the caspase-3/GSDME pathway in both TKI-sensitive and TKI-resistant CML cells. In a CML mouse model, this combination therapy significantly suppressed tumorigenesis and triggered a robust antitumor immune response, facilitating the clearance of leukemic cells. Furthermore, the 5-FU@HFn NPs exhibited excellent in vivo safety.

conclusionsThe innovative therapeutic strategy, combining 5-FU@HFn nanoparticles with low-dose DAC, effectively induces caspase-3/GSDME-mediated pyroptosis and activates antitumor immunity for CML. This approach offers a potential alternative for patients resistant or intolerant to TKIs.

Indexed as

Antineoplastic AgentsDecitabineFluorouracilImmunotherapyLeukemia, Myelogenous, Chronic, BCR-ABL PositivePyroptosisAnimalsCaspase 3Cell Line, TumorGasderminsHumansMiceMice, Inbred BALB CNanoparticlesAntineoplastic AgentsCaspase 3DecitabineFluorouracilGasderminsGSDME protein, human5-fluorouracilAntitumor immunityChronic myeloid leukemiaFerritin nanocagePyroptosis

Identifiers

PMID40148810
PMCPMC11951746

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.