Abstract
Leukemia is a common and lethal disease. In recent years, iron-based nanomedicines have been developed as a new ferroptosis inducer to leukemia. However, the cytotoxicity of iron nanoparticles to leukemia cells at the transcriptomic level remains unclear. This study investigated the effects of two kinds of iron nanoparticles, 2,3-Dimercaptosuccinic acid (DMSA)-coated Fe3O4 nanoparticles (FeNPs) as a reactive oxygen species (ROS) inducer and Prussian blue nanoparticles (PBNPs) as an ROS scavenger, on the transcriptomic profiles of two leukemia cells (KG1a and HL60) by RNA-Seq. As a result, 470 and 1690 differentially expressed genes (DEGs) were identified in the FeNP-treated HL60 and KG1a cells, respectively, and 2008 and 2504 DEGs were found in the PBNP-treated HL60 and KG1a cells, respectively. Among them, 14 common upregulated and 4 common downregulated DEGs were found, these genes were representative genes that play key roles in lipid metabolism (GBA and ABCA1), iron metabolism (FTL, DNM1, and TRFC), antioxidation (NQO1, GCLM, and SLC7A11), vesicle traffic (MCTP2, DNM1, STX3, and BIN2), and innate immune response (TLR6, ADGRG3, and DDX24). The gene ontology revealed that the mineral absorption pathway was significantly regulated by PBNPs in two cells, whereas the lipid metabolism and HIF-1 signaling pathways were significantly regulated by FeNPs in two cells. This study established the gene signatures of two kinds of nanoparticles in two leukemia cells, which revealed the main biological processes regulated by the two kinds of iron nanoparticles. These data shed new insights into the cytotoxicity of iron nanoparticles that differently regulate ROS in leukemia cells with variant stemness.
Highlights
Leukemia, especially acute myeloid leukemia (AML), is a lethal disease characterized by the accumulation of DNA-damaged immature myeloid precursors [1]
The Prussian blue nanoparticles (PBNPs) were at sizes of 152 nm and had potentials of −1.94, while the Fe3O4 nanoparticles (FeNPs) were at sizes of 20 nm and had potentials of −20.9 (Figure 1A,B)
This study provided the transcriptomic profiles of two leukemia cells (KG1a and HL60) that had different stemness treated by two kinds of iron nanoparticles (FeNPs and PBNPs) that had different reactive oxygen species (ROS) regulation capabilities
Summary
Especially acute myeloid leukemia (AML), is a lethal disease characterized by the accumulation of DNA-damaged immature myeloid precursors [1]. The development of nanomedicines as ferroptosis inducer in cancer cells has become a new promising approach to leukemia [4,5,6]. Ferroptosis can be stimulated by the GPX4 inhibitors (erastin, sorafenib, altretamine, etc.) and reagents that cause cellar iron overload (FeCl2, salinomycin, and hemoglobin), which leads to fueled ROS production and inhibition of tumor growth [8,9,10,11]. These compounds have already been challenged by the same resistance problem as that of traditional cancer drugs [12]. A nanoparticle iron supplement, ferumoxytol, was found to have an antileukemia effect in vitro and in vivo in leukemia cells with a low level of ferroportin (FPN) by inducing ferroptosis [14]
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