Evidence map›Paper›PMID 40685918›Full record

ArticleAdvanced healthcare materials2025

Suppressing t(4;11) Acute Leukemia by Lipopolymer Nanoparticle Delivery of siRNA Targeting KMT2A::AFF1 with Enhanced Extrahepatic Delivery.

Mohammad Nasrullah, Remant Kc, Amarnath Praphakar Rajendran, Saba Abbasi Dezfouli, Cezary Kucharski, Xiaoyan Jiang, Spencer B Gibson, Joseph Brandwein, Olaf Heidenreich, Hasan Uludağ

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced healthcare materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

10 authors.

Mohammad NasrullahFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H1, Canada.ORCID 0000-0003-1346-355X
Remant KcDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 1R1, Canada.
Amarnath Praphakar RajendranDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 1R1, Canada.
Saba Abbasi DezfouliDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 1R1, Canada.
Cezary KucharskiDepartment of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, T6G 1R1, Canada.
Xiaoyan JiangDepartment of Medical Genetics, Terry Fox Laboratory, British Columbia Cancer Research Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Spencer B GibsonDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, T6G 1Z2, Canada.ORCID 0000-0003-0119-732X
Joseph BrandweinDivision of Hematology, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, T6G 2B7, Canada.
Olaf HeidenreichPrincess Maxima Center for Pediatric Oncology, Utrecht, CS, 3584, The Netherlands.ORCID 0000-0001-5404-6483
Hasan UludağFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H1, Canada.ORCID 0000-0002-1118-4170

Funding

Alex's Lemonade Stand FoundationCanadian Cancer Society Canadian Cancer Society 2023 Challenge Grant (CHA-24)Cancer Research Institute of Northern Alberta 2023RachelMandelScholarshipinLymphomaandOtherBloodCancersCIHREdmonton Civic Employees Charitable Assistance FundMitacsNatural Sciences and Engineering Council of Canada
6 · The paper itself

Abstract

Effective siRNA delivery in acute lymphoblastic leukemia (ALL) is limited by preferential hepatic accumulation. To address this, a lipopolymer (PEI-C) is developed by conjugating lipid to polyethylenimine and formulated lipopolymer nanoparticles (LPNPs) via complexation with siRNA. The siRNA delivery efficiency of LPNPs is evaluated in vitro in t(4;11)-positive ALL cells (RS4;11 and SEM) as well as "normal" peripheral blood mononuclear cells (PBMCs) from human donors and bone marrow stromal cells (BMSCs) from mice. Molecular effects are assessed by quantifying target mRNA silencing and downstream apoptosis. In vivo biodistribution and therapeutic efficacy are examined in mouse models. LPNPs demonstrated significantly higher siRNA uptake than commercial reagents in PBMCs and BMSCs, reaching siRNA uptakes of 87.2% and 93.0% in RS4;11 and SEM cells, respectively. Molecular analyses revealed effective silencing of KMT2A::AFF1 mRNA (≈80% in RS4;11), accompanied by BCL2 downregulation and increased apoptosis. In vivo, LPNPs showed efficient siRNA biodistribution to leukemia-associated organs (spleen and bone marrow) and significantly reduced leukemia burden in a systemic RS4;11 xenograft mouse model and improved survival. These findings suggest that PEI-C-formulated LPNPs present a promising avenue for therapeutic siRNA delivery in ALL, effectively targeting leukemia-associated organs, and warrant further exploration in clinical studies.

Indexed as

DNA-Binding ProteinsHistone-Lysine N-MethyltransferaseMyeloid-Lymphoid Leukemia ProteinNanoparticlesPrecursor Cell Lymphoblastic Leukemia-LymphomaRNA, Small InterferingAnimalsApoptosisCell Line, TumorHumansLipidsMicePolyethyleneimineTissue DistributionDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseLipidsMyeloid-Lymphoid Leukemia ProteinPolyethyleneimineRNA, Small InterferingKMT2A::AFF1leukemialipopolymer nanoparticleLPNPMLL‐AF4siRNA

Identifiers

PMID40685918
PMCPMC12538540

What OpenQuestion holds

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Registered trials

None linked

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.