Brush-arm star polymer imaging agents and uses thereof

1. A brush-arm star polymer comprising one or more repeating units of Formula (I) and one or more repeating units of Formula (II):

or a salt thereof, wherein:

the combined number of repeating units of Formula (I) and repeating units of Formula (II) is at least 100;

each A is independently C 1 -C 12 alkylene or C 1 -C 12 heteroalkylene, wherein each of the alkylene and heteroalkylene is independently optionally substituted with 1-2;

each A 1 is C 1 -C 12 heteroalkylene, wherein each of the heteroalkylene is independently optionally substituted with 1-2 oxo;

each B is C 1 -C 12 alkylene, wherein each of the alkylene is independently optionally substituted with one oxo;

each X is an imaging agent, wherein at least one imaging agent is an organic nitroxide radical-containing imaging agent;

each P is a polyethylene glycol;

each instance of L is independently selected from the group consisting of C 1 -C 12 alkylene, C 1 -C 12 heteroalkylene, (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 alkylene)-heteroarylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-heteroarylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-heteroarylene-(C 0 -C 12 heteroalkylene), and a combination of any two thereof;

 wherein:

each of the alkylene, heteroalkylene, arylene, and heteroarylene is independently optionally substituted with 1-24 independently selected R 1 selected from the group consisting of alkyl, heteroalkyl, halo, cyano, oxo, nitro, —OR A , —N(R A ) 2 , —NR A C(O)R A , —NR A C(O)OR A , —NR A C(O)N(R A ) 2 , —C(O)N(R A ) 2 , —C(O)R A , —C(O)OR A , —OC(O)R A , —OC(O)OR A , —OC(O)N(R A ) 2 , —SR A , and —S(O) m R A ;

each of the heteroarylene is independently monocyclic, 5- or 6-membered heteroarylene;

each R A is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, or C 1 -C 6 haloalkyl;

each m is independently 1 or 2; and

each of p and o are independently an integer between 0 and 20, inclusive;

each of a and b is 1;

when “1”, “2”, “3”, “4”, “5”, and/or “6” shown in Formula (I) or Formula (II) are terminal groups, the terminal groups are independently selected from the group consisting of optionally substituted alkenyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; and

each y is independently an integer between 1 and 100, inclusive.

2. The brush-arm star polymer of claim 1 , wherein P is a polyethylene glycol with a number average molecular weight about 2000, about 2500, about 3000, about 3500, or about 4000, g/mol.

3. The brush-arm star polymer of claim 1 , wherein:

each B is C 1 -C 12 alkylene, wherein each of the alkylene is substituted with one.

4. The brush-arm star polymer of claim 1 , wherein each L of Formula (I) is independently selected from

5. The brush-arm star polymer of claim 1 , wherein when the brush-arm star polymer comprises two or more imaging agents, at least one imaging agent is a chelated metal, inorganic compound, or organic compound, or a salt thereof.

6. The brush-arm star polymer of claim 1 , wherein at least one organic nitroxide radical-containing imaging agent is of the formula:

7. The brush-arm star polymer of claim 1 ,

wherein:

each instance of L of Formula (I) is independently C 1 -C 12 alkylene, C 1 -C 12 heteroalkylene, (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 alkylene)-heteroarylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-heteroarylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-heteroarylene-(C 0 -C 12 heteroalkylene), or a combination of any two thereof, wherein each of the alkylene, heteroalkylene, arylene, and heteroarylene is independently optionally substituted with 1-24 independently selected R 1 selected from the group consisting of alkyl, heteroalkyl, halo, cyano, oxo, nitro, —OR A , —N(R A ) 2 , NR A C(O)R A , —NR A C(O)OR A , —NR A C(O)N(R A ) 2 , —C(O)N(R A ) 2 , —C(O)R A , —C(O)OR A , —OC(O)R A , —OC(O)OR A , —OC(O)N(R A ) 2 , —SR A , and —S(O) m R A .

8. The brush-arm star polymer of claim 1 , wherein at least one repeating unit of Formula (I) is of formula:

9. The brush-arm star polymer of claim 1 ,

wherein:

each instance of L of Formula (I) is independently C 1 -C 12 alkylene, C 1 -C 12 heteroalkylene, (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 alkylene)-heteroarylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-heteroarylene-(C 0 -C 12 alkylene), (C 0 -C 12 heteroalkylene)-heteroarylene-(C 0 -C 12 heteroalkylene), or a combination of any two thereof, wherein each of the alkylene, heteroalkylene, arylene, and heteroarylene is independently optionally substituted with 1-24 independently selected R 1 selected from the group consisting of alkyl, heteroalkyl, halo, cyano, oxo, nitro, and —OR A .

10. The brush-arm star polymer of claim 1 , wherein the repeating unit of Formula (II) is of formula:

11. The brush-arm star polymer of claim 1 , wherein the ratio of repeating unit of Formula (I) and repeating unit of Formula (II) is between about 1:20 to about 20:1, respectively.

12. A method of producing a brush-arm star polymer of claim 1 comprising:

(a) reacting one or more macromonomers of Formula (III):

or a salt thereof, with a metathesis catalyst to form a living polymer; and

(b) mixing a crosslinker of Formula (IV):

or a salt thereof, with the living polymer.

13. A method of imaging a subject, the method comprising steps of:

administering to a subject an effective amount of the polymer of claim 1 ; and

acquiring an image.

14. A method of performing magnetic resonance imaging of a subject, the method comprising steps of:

administering to a subject an effective amount of the polymer of claim 1 ; and

acquiring a magnetic resonance image;

wherein at least one imaging agent is useful for performing magnetic resonance imaging.

15. A method of performing near-infrared fluorescence imaging of a subject, the method comprising steps of:

administering to a subject an effective amount of the polymer of claim 1 ; and

acquiring a near-infrared fluorescence image;

wherein at least one imaging agent is useful for performing near-infrared fluorescence imaging.

16. The brush-arm star polymer of claim 1 , wherein each P is polyethylene glycol with a number average molecular weight ranging from about 200 g/mol to about 6000 g/mol, inclusive.

17. The brush-arm star polymer of claim 1 , wherein each L of Formula (II) is of the formula:

wherein each q is independently an integer between 0 and 20, inclusive.

18. The brush-arm star polymer of claim 1 , wherein each A is C 1 -C 12 heteroalkylene, wherein each of the heteroalkylene is optionally substituted with 1-2.

19. The brush-arm star polymer of claim 1 , wherein each y is 1.

20. The brush-arm star polymer of claim 5 , wherein at least one imaging agent is a near-infrared fluorescence imaging agent.

21. The brush-arm star polymer of claim 5 , wherein at least one imaging agent is of the formula:

22. The brush-arm star polymer of claim 5 , wherein at least one repeating unit of Formula (I) is of formula:

23. The brush-arm star polymer of claim 1 , wherein the brush-arm star polymers form a particle of a diameter between about 10 nm and about 1000 nm, inclusive.

24. The brush-arm star polymer of claim 1 , wherein each A 1 is C 1 -C 12 heteroalkylene, wherein each of the heteroalkylene is substituted with 1-2.

25. The brush-arm star polymer of claim 1 , wherein each L of Formula (II) is independently (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 alkylene), (C 0 -C 12 alkylene)-arylene-(C 0 -C 12 heteroalkylene), (C 0 -C 12 heteroalkylene)-arylene-(C 0 -C 12 heteroalkylene), or a combination of any two thereof, wherein each of the alkylene, heteroalkylene, and arylene is independently substituted with 1-24 independently selected R 1 selected from the group consisting of alkyl, heteroalkyl, halo, cyano, oxo, nitro, —OR A , —N(R A ) 2 , —NR A C(O)R A , —NR A C(O)OR A , —NR A C(O)N(R A ) 2 , —C(O)N(R A ) 2 , —C(O)R A , —C(O)OR A , —OC(O)R A , —OC(O)OR A , —OC(O)N(R A ) 2 , —SR A , and —S(O) m R A .