Liposome compositions and methods of use thereof

1. A liposome comprising a pHLIP polypeptide, wherein a hydrophobic region of the lipid bilayer of said liposome is substantially free of said pHLIP polypeptide, wherein said lipid bilayer comprises a polyethylene glycol (PEG)-phospholipid, and wherein said pHLIP polypeptide is attached to said PEG-phospholipid.

2. The liposome of claim 1 , wherein the amino-terminal end of said pHLIP polypeptide is attached to said PEG-phospholipid and the carboxy-terminal end of said pHLIP polypeptide is located outside of said liposome.

3. The liposome of claim 1 , wherein the carboxy-terminal end of said pHLIP polypeptide is attached to said PEG-phospholipid, and the amino-terminal end of said pHLIP polypeptide is located outside of said liposome.

4. The liposome of claim 1 , wherein said liposome further comprises a cargo inside of said liposome or inside of said lipid bilayer.

5. The liposome of claim 4 , wherein said cargo comprises a therapeutic compound.

6. The liposome of claim 4 , wherein said cargo comprises a polar composition.

7. The liposome of claim 1 , wherein said liposome further comprises a hydrophobic cargo incorporated into said lipid bilayer.

8. The liposome of claim 1 , wherein said liposome further comprises a lipid bilayer-tethered cargo.

9. The liposome of claim 8 , wherein said tethered cargo is attached to a lipid by a cleavable or non-cleavable bond.

10. The liposome of claim 8 , wherein said tethered cargo is attached to a lipid by a S—S bond.

11. A method of delivering a cargo into a target cell comprising contacting said target cell with cargo-loaded pHLIP+ liposome according to claim 1 , a lipid bilayer of said liposome being substantially free of said pHLIP polypeptide, wherein at least 10% more of said cargo is delivered to the cytoplasm of said target cell compared to the amount delivered using pHLIP-liposome.

12. The method of claim 11 , wherein said target cell is characterized by a microenvironment comprising a low pH.

13. The method of claim 11 , wherein said pHLIP+ liposome fuses with a cell membrane of said target cell.

14. The method of claim 11 , wherein said pHLIP+ liposome both fuses with a cell membrane of said target cell and is taken up by said cell by endocytosis.

15. The method of claim 11 , wherein said pHLIP+ liposome preferentially fuses with a membrane of an endosomal compartment and a lysosomal compartment of said target cell after uptake by endocytosis.

16. The method of claim 11 , wherein said target cell is a tumor cell, ischemic cell, inflamed cell, bacterially-infected cell, fungus-infected cells, or virally-infected cell.

17. The method of claim 11 , wherein said cargo comprises ceramide, a deoxyribonucleotide (DNA) binding agent, a small interfering ribonucleic acid (RNA), a DNA, a polar toxin, an inhibitor, TAXOL®, or doxorubicin.

18. A pharmaceutical composition comprising the liposome of claim 1 .