Nanodrug targeting protein geranylgeranylation

1. A liposome, which is

A basic liposome, or

a transferrin-conjugated liposome, or

a pH-sensitive liposome,

wherein the liposome encapsulates a compound having the formula

wherein J is hydrogen or is 1-2 substituents independently selected from the group consisting of halogen, C1-C3 alkyl, OR′, SR′, and NR′2, where R′ is alkyl,

wherein G is

wherein E is hydrogen or is 1-2 substituents selected from the group consisting of halogen, C1-C3 alkyl, OR′, SR′, and NR′2, where R′ is alkyl,

wherein W is selected from the group consisting of hydrogen, cyclic, linear, or branched alkyl of from 2 to 8 carbons, unsubstituted phenyl. and phenyl substituted with C1-C3 alkyl, halogen, OR′, SR′, and NR′2, where R′ is alkyl,

wherein

is selected from the group consisting of

wherein A is selected from the group consisting of:

wherein M is selected from the group consisting of OH, OR″, NH2, NHOH, NHOR″, wherein R″ is methyl or ethyl, or any other group that has a polar metal binder

wherein R corresponds to an alpha-substituent of natural or non-natural alpha-amino acid;

wherein Z is S—U: and

wherein U is selected from the group consisting of alkyl having 10 or fewer carbons, phenyl, optionally substituted with halogen or OR″, wherein R″ is methyl or ethyl, and (CH2)n-COOR4, wherein n=1-4 and R4 is a linear or branched alkyl having four or fewer carbons;

or the compound P61-A7.

2. The liposome of claim 1 , wherein A is

3. The liposome of claim 1 , wherein A is

4. The liposome of claim 1 , wherein A is

5. The liposome of claim 1 , wherein M is OEt, OMe, Ot-Bu, OH, NH2, NHOH, NHOMe, or any other groups that have a polar metal binder.

6. The liposome of claim 1 , wherein the compound is selected from the group consisting of

7. The liposome of claim 1 , wherein G is

8. The liposome of claim 1 , which inhibits the activity of a protein prenyltransferase.

9. The liposome of claim 1 , which inhibits the activity of a RabGGTase.

10. The liposome of claim 1 , which inhibits the activity of GGTase I.

11. The liposdome of claim 1 , which inhibits the activity of GGTase I and RabGGTase.

12. A method comprising administering the liposome of claim 1 to a cell in an amount sufficient to inhibit the activity of GGTase I and/or RabGGTase.

13. The method of claim 12 , wherein the liposome is administered at a microgram/ml concentration.

14. A method comprising administering a liposome of claim 1 in an amount sufficient to inhibit the growth of a cancer cell or to reduce the size of a tumor of cancer cells.

15. The method of claim 14 , wherein the cancer cell comprises GGTase I and/or RabGGTase modified proteins.

16. A method comprising administering to a subject in need of treatment for a cancer the liposome of claim 1 in an amount sufficient to inhibit the activity of a protein prenyltransferase.

17. The method of claim 16 , wherein the protein prenyltransferase is GGTase I, RabGGTase, or both.

18. The method of claim 16 , wherein the cancer cell comprises GGTase I and/or RabGGTase modified proteins.

19. The method of claim 16 , further comprising administering to the subject an inhibitor of farnesyltransferase (FT), wherein the liposome and the FT inhibitor together are in an amount sufficient to inhibit the growth of a cancer cell or to reduce the size of a cancerous tumor.

20. A method comprising measuring the GGTase I and/or RabGGTase inhibiting activity of a liposome of claim 1 .

21. A method of preparing a liposome of claim 1 , comprising introducing a solution comprising the compound into a vessel containing a preformed liposome, collecting the loaded liposome by centrifugation, and resuspending the collected liposome in a suitable buffer.

22. A kit comprising a liposome of claim 1 , in a container.

23. A method of delivering the liposome of claim 1 to a patient in need thereof, the method comprising:

registering in a computer readable storage medium the identity of a physician permitted to prescribe the liposome;

providing the patient with counseling information concerning a risk attendant to the liposome;

obtaining informed consent of the patient to receive the liposome despite the risk;

registering the patient in the computer readable medium after obtaining the informed consent; and

permitting the patient access to the liposome.

24. The liposome of claim 1 , which is a pH-sensitive liposome, wherein the liposome comprises a ratio of the two lipids POPC and DSPE-PG8MG of about 85/15, and wherein the liposome is sensitive to a pH of about 6.0 or lower.

25. A compound or salt thereof having the formula

or a pharmaceutical composition thereof which also comprises a pharmaceutically acceptable carrier.