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Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted MiR-150 Nanoparticles

Abstract

Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3-overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3 We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150-based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. Cancer Res; 76(15); 4470-80. ©2016 AACR.

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References
1.
Hong S, Leroueil P, Janus E, Peters J, Kober M, Islam M . Interaction of polycationic polymers with supported lipid bilayers and cells: nanoscale hole formation and enhanced membrane permeability. Bioconjug Chem. 2006; 17(3):728-34. DOI: 10.1021/bc060077y. View

2.
He L, Hannon G . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31. DOI: 10.1038/nrg1379. View

3.
Leung A, Man C, Kwong Y . FLT3 inhibition: a moving and evolving target in acute myeloid leukaemia. Leukemia. 2012; 27(2):260-8. DOI: 10.1038/leu.2012.195. View

4.
Dohner H, Weisdorf D, Bloomfield C . Acute Myeloid Leukemia. N Engl J Med. 2015; 373(12):1136-52. DOI: 10.1056/NEJMra1406184. View

5.
Liu X, Rocchi P, Qu F, Zheng S, Liang Z, Gleave M . PAMAM dendrimers mediate siRNA delivery to target Hsp27 and produce potent antiproliferative effects on prostate cancer cells. ChemMedChem. 2009; 4(8):1302-10. DOI: 10.1002/cmdc.200900076. View