Gamma-Fe2O3 nanoparticles increase therapeutic efficacy of combination with paclitaxel and anti-ABCG2 monoclonal antibody on multiple myeloma cancer stem cells in mouse model

Abstract

Cancer stem cells (CSCs) are thought to be responsible for the relapse of multiple myeloma (MM). The objective of this study was to target therapy of MM cancer stem cells using gamma-Fe2O3@DMSA magnetic nanoparticle combination with paclitaxel and anti-ABCG2 monoclonal antibody, and to evaluate the combined therapeutic efficacy. CSCs were isolated from human MM cell line RPMI 8226 based on negative expression of CD138 and CD34. In vivo and in vitro studies demonstrated that the isolated CD138-CD34- cells displayed certain stem cell characteristics, including significant increase in expression of ABCG2 transporter, proliferation, mobility, drug resistance, clonogenic potential in soft agar media and tumorigenecity in mice. Treatment with nanoparticles, paclitaxel and anti-ABCG2 antibody remarkably inhibited the growth of CD138-CD34- cells in vitro and their derived tumors in xenografts. The inhibition was also correlated with elevated expression of caspase-9, caspase-8 and caspase-3, and down-regulation of NF-KB. Our data indicate that the nanoparticle combination with paclitaxel and anti-ABCG2 monoclonal antibody offers an effective approach to treatment of MM CSCs through an apoptotic pathway.