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

Patent metadata

Field	Value
Publication number	US-11951178-B2
Application number	US-202117375548-A
Country	US
Kind code	B2
Filing date	Jul 14, 2021
Priority date	Jun 14, 2016
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

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 method of treating acute myeloid leukemia (AML) in a patient in need thereof, the method comprising: administering to the patient an FLT3-guided dendrimeric nanoparticle complexed with miR-150, wherein the FLT3-guided dendrimeric nanoparticle comprises a PAMAM dendrimer that is surface-functionalized with a ligand specific for FLT3 receptor, said ligand consists of a natural and/or synthetic FLT3L peptide having at least 90% sequence homology to SEQ ID NO: 1.

2. The method according to claim 1 , wherein the AML is characterized by overexpression of FLT3.

3. The method according to claim 1 , wherein the ligand consists of a synthetic FLT3L peptide having an amino acid sequence as set forth in SEQ ID NO: 1.

4. The method according to claim 1 , wherein the PAMAM dendrimer comprises a G2, G3, G4, G5, G6, G7, or G8-dendrimer.

5. The method according to claim 4 , wherein the PAMAM dendrimer comprises a G7-dendrimer.

6. The method according to claim 1 , wherein the miR-150 comprises a stability modification.

7. The method according to claim 6 , wherein the stability modification of miR-150 comprises 2′-O methylation.

8. The method according to claim 1 , wherein the complexed nanoparticle is G7-Flt3L-(2′OMe)miR-150.

9. The method according to claim 1 , wherein administering comprises systemic administration.

10. The method according to claim 9 , wherein systemic administration comprises intravenous administration.

11. The method according to claim 1 , further comprising administering at least one bromodomain and extra terminal motif (BET) protein inhibitor.

12. The method according to claim 11 , wherein the BET inhibitor targets both BD1 and BD2.

13. The method according to claim 11 , wherein the BET inhibitor is selected from the group consisting of JQ1, I-BET 151, I-BET 762, OTX-015, TEN-010, CPI-201, CPI-0610, and combinations thereof.

14. The method according to claim 13 , wherein the BET inhibitor comprises JQ1.

15. The method according to claim 11 , wherein the FLT3-guided dendrimer nanoparticle complexed with miR-150 is administered before the BET inhibitor.

16. The method according to claim 11 , wherein the FLT3-guided dendrimer nanoparticle complexed with miR-150 is administered after the BET inhibitor.

Assignees

• Univ Cincinnati
• Univ Illinois
• Univ Chicago
• Univ Chicago

Inventors

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

Classifications

• A61K47/6935 Primary

  the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol · CPC title

• A61K31/551

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

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K38/19 Primary

  Cytokines; Lymphokines; Interferons · CPC title

• A61K45/06

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