Theranostic nucleic acid binding fluorescent nanoprobes and uses thereof

Patent metadata

Field	Value
Publication number	US-11779661-B2
Application number	US-201716348572-A
Country	US
Kind code	B2
Filing date	Nov 8, 2017
Priority date	Nov 10, 2016
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

Abstract

The present disclosure provides nucleic acid binding nanoprobes having one or more fluorochromes and a polymer, where each of the fluorochromes is connected to the polymer, and methods of using the same.

First claim

What is claimed is:

1. A nucleic acid binding nanoprobe having structure of Formula I:

or a pharmaceutically acceptable salt thereof;
wherein:
each L 1 is independently C 2-20 alkylene;
each L 2 is independently C 2-20 alkylene, wherein any of the carbons in the C 2-20 alkylene chain is optionally replaced with C(O), O, S, S(O), S(O) 2 , NR a1 NR b1 C(O), or a triazole;
P 1 is a polysaccharide;
each R 1 is independently (CH) t -5-10 membered heteroaryl, (CH) u -5-10 membered heterocycloalkyl, C 6-10 aryl, or NR a2 R b2 ; wherein each 5-10 membered heteroaryl and 5-10 membered heterocycloalkyl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming N or S atoms; and wherein the C 6-10 aryl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, NH 2 , NH(C 1-6 alkyl), and N(C 1-6 alkyl) 2 ;
or two R 1 adjacent to each other and together with the carbon atoms to which they are attached form an C 6-10 aryl; wherein the C 6-10 aryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl, NH 2 , NH(C 1-6 alkyl), and N(C 1-6 alkyl) 2 ;
R 2 and R 3 are independently selected from H and C 1-6 alkyl;
each R a1 , R b1 , R a2 , and R b2 is independently selected from H and C 1-6 alkyl;
m is 1, 2, 3, or 4;
t is 1, 2, 3, 4, 5, or 6;
u is 1, 2, 3, 4, 5, or 6;
x is about 2 to about 20, and
wherein the nanoprobe does not comprise a metal.

2. The nanoprobe of claim 1 , wherein each L 1 is independently C 3-6 alkylene.

3. The nanoprobe of claim 1 , wherein each L 2 is independently C 10-20 alkylene, wherein any of the carbons in the C 10-20 alkylene chain is optionally replaced with C(O), O, NR a1 NR b1 C(O), or a triazole.

4. The nanoprobe of claim 1 , wherein the polysaccharide is about 5 to about 120 kDa in mass.

5. The nanoprobe of claim 1 , wherein the polysaccharide is dextran, pullulan, dextrin, hydroxyethyl starch.

6. The nanoprobe of claim 1 , wherein each R 1 is independently (CH) t -5-10 membered heteroaryl or (CH) u -5-10 membered heterocycloalkyl.

7. The nanoprobe of claim 1 , wherein R 2 and R 3 are C 1-6 alkyl.

8. The nanoprobe of claim 1 , wherein m is 1 or 2.

9. The nanoprobe of claim 1 , wherein x is 3, 4, 5, 6, 7, or 8.

10. The nanoprobe of claim 1 , wherein the moiety

is selected from:

11. The nanoprobe of claim 1 , wherein the nanoprobe is

or a pharmaceutically acceptable salt thereof;
wherein x is 2 or 3; P 1 is dextran, wherein the dextran is about 40 kDa in mass.

12. The nanoprobe of claim 1 , wherein x is about 2 to about 10.

13. The nanoprobe of claim 1 , wherein the nanoprobe is about 40 to about 1000 kDa in mass.

14. The nanoprobe of claim 1 , wherein the nanoprobe is about 4 to about 10 nm in diameter.

Assignees

• Massachusetts Gen Hospital

Inventors

• Sosnovik David
• Josephson Lee
• Chen Howard

Classifications

• A61K49/0054 Primary

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• A61K47/6929

  the form being a nanoparticle, e.g. an immuno-nanoparticle · CPC title

• A61K49/0021

  the fluorescent group being a small organic molecule · CPC title

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title