Brush-poly (glycoamidoamine)-lipids and uses thereof

1. A polymer of the formula:

or a salt thereof, wherein:

each instance of X A is independently substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, —OR XA , —N(R XA ) 2 , —SR XA , —C(═NR XA )R XA , —C(═NR XA )OR XA , —C(═NR XA )N(R XA ) 2 , —C(═O)R XA , —C(═O)OR XA , or —C(═O)N(R XA ) 2 , wherein each instance of R XA is independently hydrogen, substituted acyl, unsubstituted acyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R XA are joined to form a substituted heterocyclic ring, unsubstituted heterocyclic ring, substituted heteroaryl ring, or unsubstituted heteroaryl ring;

each instance of Y A is independently ═O, ═S, or ═NR YA , wherein each instance of R YA is independently hydrogen, substituted C 1-6 alkyl, unsubstituted C 1-6 alkyl, or a nitrogen protecting group;

each instance of R A is independently hydrogen, a moiety of the formula:

 or a moiety of the formula:

 provided that at least about 60% of the total instances of R A are of the formula:

 wherein:

each instance of R A1 is independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkenyl, or unsubstituted alkenyl;

each instance of R A2 is independently hydrogen substituted alkyl, or unsubstituted alkyl; and

each instance of R A3 is independently hydrogen substituted alkyl, or unsubstituted alkyl;

each instance of a is 1, 2, 3, 4, or 5;

each instance of k is 1, 2, 3, 4, 5, or 6;

each instance of u is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

p is an integer between 1 and 1000, inclusive.

2. The polymer of claim 1 , wherein the polymer is of the formula:

or a salt thereof.

3. The polymer of claim 1 , wherein the polymer is of the formula:

or a salt thereof.

4. The polymer of claim 1 , wherein the polymer is of the formula:

or a salt thereof.

5. The polymer of claim 1 , or a salt thereof, wherein each instance of R A is independently H, a moiety of the formula:

or a moiety of the formula:

provided that at least one instance of R A is of the formula:

wherein each instance of R A1 is independently unsubstituted C 4-18 alkyl.

6. The polymer of claim 1 , or a salt thereof, wherein at least one instance of X A is —OR XA or —N(R XA ) 2 .

7. The polymer of claim 1 , or a salt thereof, wherein at least about 60% of the total instances of R A are independently of the formula:

8. The polymer of claim 1 , or a salt thereof, wherein each instance of R A1 is independently substituted C 1-30 alkyl, unsubstituted C 1-30 alkyl, substituted C 2-30 alkenyl, or unsubstituted C 2-30 alkenyl.

9. The polymer of claim 1 , or a salt thereof, wherein each instance of R A2 is hydrogen.

10. The polymer of claim 1 , or a salt thereof, wherein each instance of R A3 is hydrogen.

11. The polymer of claim 1 , or a salt thereof, wherein each instance of a is 1 or 2.

12. The polymer of claim 1 , or a salt thereof, wherein each instance of k is 1, 2, 3, or 4.

13. The polymer of claim 1 , or a salt thereof, wherein each instance of u is 2, 3, or 4.

14. The polymer of claim 1 , or a salt thereof, wherein p is an integer between 1 and 30, inclusive.

15. A polymer of the formula:

or a salt thereof, wherein:

each instance of X B is independently substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, —OR XB , —N(R XB ) 2 , —SR XB , —CN, —SCN, —C(═NR XB )R XB , —C(═NR XB )OR XB , —C(═NR XB )N(R XB ) 2 , —C(═O)R XB , —C(═O)OR XB , or —C(═O)N(R XB ) 2 , —NO 2 , —NR XB C(═O)R XB , —NR XB C(═O)OR XB , —NR XB C(═O)N(R XB ) 2 , —OC(═O)R XB , —OC(═O)OR XB , or —OC(═O)N(R XB ) 2 , wherein each instance of R XB is independently hydrogen, substituted acyl, unsubstituted acyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R XB are joined to form a substituted heterocyclic ring, unsubstituted heterocyclic ring, substituted heteroaryl ring, or unsubstituted heteroaryl ring;

each instance of Y B is independently ═O, ═S, or ═NR YB , wherein each instance of R YB is independently hydrogen, substituted C 1-6 alkyl, unsubstituted C 1-6 alkyl, or a nitrogen protecting group;

each instance of R B is independently hydrogen or a moiety of the formula:

 provided that at least about 60% of the total instances of R B are of the formula:

 wherein each instance of R B1 is independently substituted alkyl, unsubstituted alkyl, substituted alkenyl, or unsubstituted alkenyl;

each instance of b is 1, 2, 3, 4, or 5;

each instance of m is 1, 2, 3, 4, 5, or 6;

each instance of v is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

q is an integer between 1 and 1000, inclusive.

16. A polymer of the formula:

or a salt thereof, wherein:

each instance of X C is independently substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, —OR XC , —N(R XC ) 2 , —SR XC , —CN, —SCN, —C(═NR XC )R XC , C(═NR XC )OR XC , —C(═NR XC )N(R XC ) 2 , —C(═O)R XC , —C(═O)OR XC , or —C(═O)N(R XC ) 2 , —NO 2 , —NR XC C(═O)R XC , —NR XC C(═O)OR XC , —NR XC C(═O)N(R XC ) 2 , —OC(═O)R XC , —OC(═O)OR XC , or —OC(═O)N(R XC ) 2 , wherein each instance of R XC is independently hydrogen, substituted acyl, unsubstituted acyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R XC are joined to form a substituted heterocyclic ring, unsubstituted heterocyclic ring, substituted heteroaryl ring, or unsubstituted heteroaryl ring;

each instance of Y C is independently ═O, ═S, or ═NR YC , wherein each instance of R YC is independently hydrogen, substituted C 1-6 alkyl, unsubstituted C 1-6 alkyl, or a nitrogen protecting group;

each instance of R C is independently hydrogen or a moiety of the formula:

 provided that at least one instance of R C is of the formula:

 wherein:

each instance of Z is independently —O—or —NR C4 —;

each instance of R C1 is independently hydrogen, substituted alkyl, unsubstituted alkyl, substituted alkenyl, or unsubstituted alkenyl;

each instance of R C2 is independently hydrogen substituted alkyl, or unsubstituted alkyl;

each instance of R C3 is independently hydrogen substituted alkyl, or unsubstituted alkyl; and

each instance of R C4 is independently hydrogen, substituted C 1-6 alkyl, unsubstituted C 1-6 alkyl, or a nitrogen protecting group;

each instance of c is 1, 2, 3, 4, or 5;

each instance of n is 0, 1, 2, 3, 4, 5, or 6;

each instance of w is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

r is an integer between 1 and 1000, inclusive.

17. A particle comprising a polymer of claim 1 , or a salt thereof, and an agent.

18. A composition comprising:

a polymer of claim 1 , or a salt thereof;

an agent; and

optionally an excipient.

19. A method of delivering an agent to a subject or cell, the method comprising administering to the subject or contacting the cell with a composition of claim 18 .

20. The polymer of claim 1 , or a salt thereof, wherein each instance of R A1 is independently unsubstituted C 4-18 alkyl.

21. The polymer of claim 1 , wherein the polymer is prepared by reacting a poly(glycoamidoamine) and an epoxide as shown in the table below:

Poly(glycoamidoamine)

Epoxide

Polymer Number

Number

Number

TarN1C8

A1a

A2b

TarN1C10

A1a

A2c

TarN1C12

A1a

A2d

TarN1C14

A1a

A2e

TarN2C8

A1b

A2b

TarN2C10

A1b

A2c

TarN2C12

A1b

A2d

TarN2C14

A1b

A2e

TarN3C8

A1c

A2b

A1c

A2c

TarN3C12

A1c

A2d

TarN3C14

A1c

A2e

TarN4C8

A1d

A2b

TarN4C10

A1d

A2c

TarN4C12

A1d

A2d

TarN4C14

A1d

A2e

GalN2C8

A1e

A2b

GalN2C10

A1e

A2c

GalN2C12

A1e

A2d

GalN2C14

A1e

A2e

GalN3C8

A1f

A2b

GalN3C10

A1f

A2c

GalN3C12

A1f

A2d

GalN3C14

A1f

A2e

GalN4C8

A1g

A2b

GalN4C10

A1g

A2c

GalN4C12

A1g

A2d

GalN4C14

A1g

A2e

GluN1C10

A1h

A2c

GluN1C12

A1h

A2d

GluN1C14

A1h

A2e

GluN2C8

A1i

A2b

GluN2C10

A1i

A2c

GluN2C12

A1i

A2d

GluN2C14

A1i

A2e

GluN3C6

A1j

A2a

GluN3C8

A1j

A2b

GluN3C10

A1j

A2c

GluN3C12

A1j

A2d

GluN3C14

A1j

A2e

GluN4C8

A1k

A2b

GluN4C10

A1k

A2c

GluN4C12

A1k

A2d

GluN4C14

A1k

A2e

TarN1C16

A1o

A2f

TarN2C16

A1b

A2f

TarN3C16

A1c

A2f

GalN2C10″

A1q

A2c

GalN3C10″

A1r

A2c

GalN2C12″

A1q

A2d

GalN3C12″

A1r

A2d

GalN2C14″

A1q

A2e

GalN3C14″

A1r

A2e

GalN2C16″

A1q

A2f

GalN3C16″

A1r

A2f

GluN2C10″

A1t

A2c

GluN3C10″

A1u

A2c

GluN1C12″

A1s

A2d

GluN2C12″

A1t

A2d

GluN3C12″

A1u

A2d

GluN1C14″

A1s

A2e

GluN2C14″

A1t

A2e

GluN3C14″

A1u

A2e

GluN1C16″

A1s

A2f

GluN2C16″

A1t

A2f

GluN3C16″

A1u

A2f;

wherein:

the poly(glycoamidoamine) is of the formula as shown in the table below:

the epoxide is of the formula as shown in the table below:

or a salt thereof.

22. The composition of claim 18 , wherein the agent is a polynucleotide, small molecule, protein, or peptide.

23. The composition of claim 18 , wherein the agent is a polynucleotide.

24. The composition of claim 23 , wherein the polynucleotide is DNA.

25. The composition of claim 24 , wherein the DNA is is single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), plasmid DNA (pDNA), genomic DNA (gDNA), complementary DNA (cDNA), antisense DNA, chloroplast DNA (ctDNA or cpDNA), microsatellite DNA, mitochondrial DNA (mtDNA or mDNA), kinetoplast DNA (kDNA), provirus, lysogen, repetitive DNA, satellite DNA, or viral DNA.

26. The composition of claim 23 , wherein the polynucleotide is RNA.

27. The composition of claim 25 , wherein the RNA is mRNA, siRNA, single-stranded RNA (ssRNA), double-stranded RNA (dsRNA), small interfering RNA (siRNA), precursor messenger RNA (pre-mRNA), small hairpin RNA or short hairpin RNA (shRNA), microRNA (miRNA), guide RNA (gRNA), transfer RNA (tRNA), antisense RNA (asRNA), heterogeneous nuclear RNA (hnRNA), coding RNA, non-coding RNA (ncRNA), long non-coding RNA (long ncRNA or lncRNA), satellite RNA, viral satellite RNA, signal recognition particle RNA, small cytoplasmic RNA, small nuclear RNA (snRNA), ribosomal RNA (rRNA), Piwi-interacting RNA (piRNA), polyinosinic acid, ribozyme, flexizyme, small nucleolar RNA (snoRNA), spliced leader RNA, viral RNA, or viral satellite RNA.