Telodendrimer nanodiscs without apolipoprotein

1. A nanodisc without a membrane scaffold protein, the nanodisc comprising:

a telodendrimer of formula I:

(PEG) m -(A) p -L-D-(R) n   (I)

wherein

D is a dendritic polymer having a single focal point group, a plurality of branched monomer units and a plurality of end groups,

L is a bond or a linker linked to the focal point group of the dendritic polymer,

each PEG is a polyethyleneglycol (PEG) polymer, wherein each PEG polymer has a molecular weight of 1-100 kDa,

each R is independently selected from the group consisting of the end group of the dendritic polymer, a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug, such that when R is not an end group each R is linked to one of the end groups,

subscript n is an integer from 2 to 20, wherein subscript n is equal to the number of end groups on the dendritic polymer, and wherein at least half the number n of R groups are each independently selected from the group consisting of a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug,

subscript m is from 0 to 20,

subscript p is 0 or 1, and

radical A is a monomer or oligomer linked to at least two PEG groups; and

a lipid,

wherein the nanodisc does not include a membrane scaffold protein.

2. The nanodisc of claim 1 , wherein the telodendrimer has the formula Ib:

PEG-L-D-(R) n   (Ib)

wherein at least half the number n of R groups

are each an amphiphilic compound.

3. The nanodisc of claim 2 , wherein each branched monomer unit is lysine.

4. The nanodisc of claim 2 , wherein the telodendrimer is selected from the group consisting of:

wherein each branched monomer unit X is lysine.

5. The nanodise of claim 2 , wherein linker L has the formula:

6. The nanodisc of claim 2 , wherein each R is independently selected from the group consisting of cholic acid, (3α,5β,7α,12α)-7,12-dihydroxy-3-(2,3-dihydroxy-1-propoxy)-cholic acid (CA-4OH), (3α,5β,7α,12α)-7-hydroxy-3,12-di(2,3-dihydroxy-1-propoxy) -cholic acid (CA-5OH), (3α,5β,7α,12α)-7,12-dihydroxy-3-(3-amino-2-hydroxy-1-propoxy)-cholic acid (CA-3OH—NH 2 ), cholesterol formate, doxorubicin, and rhein.

7. The nanodise of claim 2 , wherein each R is cholic acid.

8. The nanodisc of claim 2 , wherein the telodendrimer is selected from the group consisting of PEG 5k -D-CA 8 and PEG 2k -D-CA 4 , wherein each dendritic polymer D is a poly(lysine) dendritic polymer.

9. The nanodisc of claim 1 , wherein the lipid is selected from the group consisting of a phospholipid, a lysolipid., cholesterol, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylglycerol, a phosphatidylserine, a phosphatidylinositol and a PEGylated lipid.

10. The nanodisc of claim 9 , wherein the lipid is selected from the group consisting of 1,2-dipahnitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine (DMPC), 1-tetra.decanoyl-2-hexadecanoyl-sn-glyeero-3-phosphocholine (MPPC), 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-distearoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DSPG), 1,2-dipalmitoyi-sn-glycero-3-phospho-1′-rac-glycerol) (DPPG),1-tetradecanoyl-2-hexadecanoyl-sn-glycero-3-phosphoglycerol (MPPG) and cholesterol.

11. The nanodisc of claim 10 , wherein the lipid is selected from the group consisting of MPPG and MPPC.

12. The nanodisc of claim 1 , further mprising a drug.

13. The nanodisc of claim 1 , wherein the nanodisc is less than about 100 run in diameter.

14. The nanodisc of claim 1 , wherein the ratio of lipid to telodendrimer is from about 5:1 to about 1:1 (w/w).

15. The nanodisc of claim 1 , wherein the ratio of lipid to telodendrimer is about 2.5:2 (w/w).

16. A method of making a nanodisc without a membrane scaffold protein, the method comprising:

forming a reaction mixture comprising a lipid and a telodendrimer, wherein the lipid:telodendrimer ratio is from about 50:1 to about 1:50 (w/w), thereby preparing

the nanodisc without a membrane scaffold. protein,

wherein the telodendrimer is of formula I:

(PEG) m -(A) p -L-D-(R) n   (I)

wherein

D is a dendritic polymer having a single focal point group, a plurality of branched monomer units and a plurality of end groups,

L is a bond or a linker linked to the focal point of the dendritic polymer,

each PEG is a polyethyleneglycol (PEG) polymer, wherein each PEG polymer has a molecular weight of 1-100 kDa,

each R is independently selected from the group consisting of the end group of the dendritic polymer, a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug, such that when R is not an end group each R is linked to one of the end groups,

subscript n is an integer from 2 to 20, wherein subscript n is equal to the number of end groups on the dendriticsolymer, and wherein at least half the number n of groups are each independently selected from the group consisting of a hydrophobic group, a hydrophilic group, an arnphiphi lie compound and a drug,

subscript m is from 0 to 20,

subscript p is 0 or 1, and

radical A is a monomer or oligomer linked to at least two PEG groups.

17. The method of claim 16 , wherein the lipid:telodendri ratio is from about 5:1 to about 1:1 (w/w).

18. The method of claim 16 , Wherein the lipid:telodendrimer ratio is about 5:2 (w/w).

19. The method of claim 16 , the reaction mixture further comprises chloroform and ethanol in a chloroform:ethanol ratio of from about 10:1 to about 1:1 (v/v).

20. The method of claim 16 , further comprising

lyophilizing the reaction mixture; and

contacting the lyophilized reaction mixture and a solvent to form a dispersed lipid-telodendrimer mixture.

21. A nanodisc without a membrane scaffold protein, the nanodisc consisting essentially of:

a telodendrimer having the formula:

PEG-L-D(R) n

wherein

D is a dendritic polymer having a single focal point group, a plurality of branched monomer units and a plurality of end groups,

L is a bond or a linker linked to the focal point group of the dendritic polymer,

each PEG is a polyethyleneglycol (PEG) polymer, wherein each PEG polymer has a molecular weight of 1-100 kDa,

each R is independently selected from the group consisting of the end group of the dendritic polymer, a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug, such that when R is not an end group each R is linked to one of the end groups, and

subscript n is an integer from 2 to 20, wherein subscript n is equal to the number of end groups on the dendritic polymer, and wherein at least half the number n of R groups are each an amphiphilic compound;

a lipid; and

a drug,

wherein the ratio of lipid to telodendrimer is from about 50:1 to about 1:50 (w/w).