Scavenger receptor class BI (SR-BI) mediates uptake of CPX-351 into K562 leukemia cells

Purpose: CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio, for the treatment of acute myeloid leukemia. The Scavenger Receptor class B type I (SR-BI) plays an important role in mediating the uptake of high-density lipoproteins. The purpose of this study is to assess the role of the cell surface lipoprotein receptor SR-BI in the uptake of CPX-351 liposomes (Jazz Pharmaceuticals) into K562 leukemia cells.Methods: K562 cells were pre-treated with 10 nM siRNA for 48 h and then treated with varying amount of CPX-351 for 24, 48 and 72 h. Cells were then collected and analyzed at 480/590 nm on a CytoFLEX Multicolour flow instrument to determine cellular uptake of daunorubicin. Experimental data were analyzed using two-way ANOVA with Bonferroni multiple comparisons. Significance was set at p < .05.Results: K562 cells pre-treated with SR-BI siRNA for 48 h had a reduced SRB1 cell surface concentration (74–85%). Addition of CPX-351 at 10–50 nM followed by me...