Methods for treating subjects suffering from acute myeloid leukemia with FLT3 ligand-targeted miR-150 nanoparticles

Patent metadata

Field	Value
Publication number	US-11097014-B2
Application number	US-201716310104-A
Country	US
Kind code	B2
Filing date	Jun 14, 2017
Priority date	Jun 14, 2016
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Univ Cincinnati
• Univ Illinois
• Univ Chicago
• Board Of Trustees Of The Univ Of Illinois

Inventors

• Chen Jianjun
• Hong Seungpyo
• Jiang Xi
• Li Zejuan

Classifications

• A61K38/19 Primary

  Cytokines; Lymphokines; Interferons · CPC title

• A61K47/595

  Polyamides, e.g. nylon (polyamino acids A61K47/62) · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title