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

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

SUBMITTER: Nasrullah M 

PROVIDER: S-EPMC12538540 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature