Apolipoprotein nanodiscs with telodendrimer

1. A nanodisc comprising:

a membrane scaffold protein;

a telodendrimer;

a lipid; and

a hydrophobic drug.

2. The nanodisc of claim 1 , wherein the membrane scaffold protein is apolipoprotein.

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

PEG - D -( R ) n

wherein

D is a dendritic polymer having a single focal group and a plurality of end groups;

PEG is polyethyleneglycol (PEG) of 1-100 kDa linked to the focal group of the dendritic polymer;

each R is independently selected from the group consisting of the end group of the dendritic polymer and an amphiphilic compound, such that when R is not an end group each A 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's are each an amphiphilic compound.

4. The nanodisc of claim 3 , wherein the dendritic polymer is a poly(lysine) dendritic polymer wherein each end group is hydroxy.

5. The nanodisc of claim 3 , wherein each amphiphilic compound is cholic acid (CA).

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

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

8. The nanodisc of claim 7 , wherein the lipid is selected from the group consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine (DMPC), 1-tetradecanoyl-2-hexadecanoyl-sn-glycero-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) (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DPPG), 1-tetradecanoyl-2-hexadecanoyl-sn-glycero-3-phosphoglycerol (MPPG) and cholesterol.

9. The nanodisc of claim 7 , wherein the lipid is DMPC.

10. The nanodisc of claim 1 , wherein the nanodisc is less than about 100 nm in size.

11. The nanodisc of claim 1 , wherein the nanodisc is less than about 10 nm in size.

12. The nanodisc of claim 1 , herein the ratio of lipid to telodendrimer is from about 200:1 to about 5:1 (w/w).

13. The nanodisc of claim 1 , wherein the ratio of lipid to telodendrimer is about 9:1 (w/w).

14. A cell-free method of making a nanodisc, the method comprising:

forming a vesicle comprising a telodendrimer and a lipid, wherein the ratio of lipid to telodendrimer is from about 500:1 to about 1:1 (w/w); and

forming a reaction mixture of the vesicle and a membrane scaffold protein in the absence of a cell, thereby preparing the nanodisc

the method further comprising

incorporating a hydrophobic drug in the reaction mixture and/or

loading the hydrophobic drug into the nanodisc.

15. The method of claim 14 , wherein the membrane scaffold protein is apolipoprotein.

16. The method of claim 14 , wherein the reaction mixture further comprises a lysate, a buffer, and a polymerase.

17. The method of claim 14 , wherein the lipid:telodendrimer are present in a ratio of about 99:1 (w/w).

18. The method of claim 14 , wherein the lipid:telodendrimer are present in a ratio of about 9:1 (w/w).

19. The nanodisc of claim 1 , wherein the hydrophobic drug is embedded within the nanodisc.