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

Abstract

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 measurement of cellular daunorubicin at 48, 48 or 72 h showed a significantly lower percentage of daunorubicin positive population compared with control K562 cells (p < .05). There was significantly less daunorubicin taken up in the SR-BI knock-down cells across all drug concentrations and at all three time points, although there were no concentration-related trends.

Conclusions: These preliminary studies suggest that SR-BI may be one potential mechanism by which CPX-351 is taken up into K562 cells.

Keywords:

• Scavenger receptor class B type I
• liposomes
• Vyxeos
• daunorubicin
• cytarabine
• myeloid leukemia

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Funding for this project was provided by College of Pharmacy and Nutrition, University of Saskatchewan, and Celator Pharmaceuticals Inc. prior to its acquisition by Jazz Pharmaceuticals.