Macromolecular chemotherapeutics

Patent metadata

Field	Value
Publication number	US-11116844-B2
Application number	US-201916577142-A
Country	US
Kind code	B2
Filing date	Sep 20, 2019
Priority date	Nov 9, 2017
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Embodiments of the invention are directed to a macromolecular chemotherapeutic. A non-limiting example of the macromolecular chemotherapeutic includes a block copolymer. The block copolymer can include a water-soluble block, a cationic block, and a linker, wherein the linker is connected to the water-soluble bock and the charged block.

First claim

What is claimed is:

1. A macromolecular chemotherapeutic, comprising:
a block copolymer comprising:
a water-soluble block,
a cationic block, the cationic block comprising a polymeric subunit comprising a polycarbonate backbone having from 4 to 8 atoms;
a linker, wherein the linker is connected to the water-soluble bock and the charged block; and
an endcap bound to the cationic block having the structure:

wherein which R8 is a long chain alkyl group, a polylactide, or a cholesterol.

2. The macromolecular chemotherapeutic of claim 1 , wherein the water-soluble block comprises polyethylene oxide.

3. The macromolecular chemotherapeutic of claim 2 , wherein the polyethylene oxide has an average molecular weight of 2000 to 20,000 daltons.

4. The macromolecular chemotherapeutic of claim 1 , wherein the linker is a cleavable linker.

5. The macromolecular chemotherapeutic of claim 3 , wherein the cleavable linker comprises an acetal or a disulfide.

6. The macromolecular chemotherapeutic of claim 1 , wherein the cationic block includes polymeric subunit comprising a polycarbonate backbone having from 6 to 8 atoms.

7. A method of inhibiting cancer stem cell growth comprising:
providing a culture of cancer cells, comprising a plurality of cancer stem cells;
incubating the cancer stem cells with a solution comprising a plurality of micelles, wherein the micelles comprise the macromolecular chemotherapeutic of claim.

8. The method of claim 7 , wherein the cationic block includes a polymeric subunit comprising a polycarbonate backbone having from 6 to 8 atoms.

9. A method of treating cancer, comprising:
administering to a mammal in need thereof an effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the chemotherapeutic of claim 1 .

10. The method of claim 9 further comprising killing cancer cells of the mammal by necrosis.

11. The method of claim 9 , wherein the water-soluble block comprises polyethylene oxide.

12. The method of claim 11 , wherein the polyethylene oxide has an average molecular weight of 2000 to 20,000 daltons.

13. The method of claim 9 , wherein the cleavable linker comprises an acetal.

14. The method of claim 9 , wherein the cleavable linker comprises a disulfide.

15. A method of synthesizing the macromolecular chemotherapeutic of claim 1 , comprising:
forming a mixture comprising a cyclic carbonyl monomer comprising a cyclic carbonyl group having a cationic sidechain with a macroinitiator selected from the group consisting of a polyethylene glycol comprising an acetal and a methoxypoly(ethylene glycol), and an organocatalyst, and
agitating the mixture at a time sufficient to form a block copolymer.

16. The method of claim 15 , wherein the mixture comprises an accelerator.

17. The method of claim 15 further comprising combining the block copolymer with a tertiary amine.

18. The method of claim 17 , wherein the tertiary amine comprises cholesterol or a cholesterol derivative.

19. The method of claim 15 , wherein the block copolymer is self-immolative at a pH less than or equal to 6.5.

Assignees

• IBM
• Agency Science Tech & Res
• Agency For Science Tech

Inventors

• Boday Dylan
• Cheng Wei
• Garcia Jeannette M
• Hedrick James
• Park Nathaniel H
• Wojtecki Rudy J
• Yang Chuan
• Yang Yiyan

Classifications

• A61K31/785 Primary

  Polymers containing nitrogen · CPC title

• C08G65/00

  Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule · CPC title

• C08G65/332

  containing carboxyl groups, or halides, or esters thereof · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• C08L71/02

  Polyalkylene oxides · CPC title