Targeting murine leukemic stem cells by antibody functionalized mesoporous silica nanoparticles

Abstract

Abstract Acute leukemia is initiated and maintained by leukemia stem cells (LSCs) and therefore there is great interest to develop innovative therapeutic approaches which target LSCs. Here we show that mesoporous silica nanoparticles (MSNs) functionalized with succinic anhydride, tagged with an anti-B220 antibody and loaded with the anthracycline daunorubicin are efficiently incorporated into murine B220-positive AML LSCs and preferentially kill these cells in comparison to B220-negative AML LSCs in vitro. Furthermore, short – term treatment of the AML LSCs with these MSNs before transplant significantly delayed leukemia development in recipient mice. These data demonstrate that targeting of AML LSCs can be improved by using functionalized and antigen directed MSNs as carriers for anti-leukemic drugs.