Methods for treating subjects suffering from acute myeloid leukemia with FLT3 ligand-targeted miR-150 nanoparticles
A nanoparticle delivery system designed for sustained delivery of microRNA-150 (miR-150) to FLT3-overexpressing acute myeloid leukemia (AML) cells, the delivery system comprising poly(amidoamine) (PAMAM) dendrimers complexed with miR-150, wherein at least one dendrimer is surface-functionalized with a ligand specific for FLT3 receptor, and methods for treating AML characterized by FLT3-overexpression are provided.
1. A nanoparticle delivery system designed for sustained delivery of microRNA-150 (miR-150) to FLT3-overexpressing acute myeloid leukemia (AML) cells, the delivery system comprising poly(amidoamine) (PAMAM) dendrimers complexed with miR-150, wherein at least one dendrimer is surface-functionalized with a ligand specific for FLT3 receptor;
wherein the ligand specific for FLT3 receptor consists of a synthetic FLT3L peptide having at least 90% sequence homology to SEQ ID NO: 1.
2. The delivery system according to claim 1 , wherein the PAMAM dendrimers comprise between generation-2 and generation-8 dendrimers.
3. The delivery system according to claim 1 , wherein the PAMAM dendrimers comprise generation 7 (G7) dendrimers.
4. The delivery system according to claim 1 wherein the synthetic FLT3L peptide is Flt3L peptide consisting of SEQ ID NO: 1.
5. The delivery system according to claim 1 , wherein the miR-150 is modified for stability.
6. The delivery system according to claim 5 , wherein the miR-150 stability modification comprises 2′-O methylation.
7. The nanoparticle delivery system according to claim 1 comprising G7-Flt3L-(2′OMe)miR-150.