Liposome compositions and methods of use thereof
The present application relates to compositions comprising and methods of using a liposome comprising a pHLIP polypeptide, wherein a lipid bilayer of the liposome is substantially free of the pHLIP polypeptide.
1. A method of delivering a cargo into a target cell comprising contacting said target cell with cargo-loaded pH (Low) Insertion Peptide (pHLIP)+ liposome, 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.
2. The method of claim 1 , wherein said target cell is characterized by a microenvironment comprising a low pH.
3. The method of claim 1 , wherein said pHLIP+ liposome fuses with a cell membrane of said target cell.
4. The method of claim 1 , wherein said pHLIP+ liposome both fuses with a cell membrane of said target cell and is taken up by said cell by endocytosis.
5. The method of claim 1 , wherein said pHLIP+ liposome preferentially fuses with a membrane of an endosomal compartment of said target cell after uptake by endocytosis.
6. The method of claim 1 , wherein said target cell is a tumor cell, ischemic cell, inflamed cell, bacterially-infected cell, fungus-infected cells, or virally-infected cell.
7. The method of claim 1 , wherein said cargo comprises a therapeutic agent.
8. The method of claim 7 , wherein said therapeutic agent comprises ceramide, a deoxyribonucleotide (DNA) binding agent, a small interfering ribonucleic acid (siRNA), a DNA, a polar toxin, an inhibitor, paclitaxel, or doxorubicin.
9. The method of claim 1 , wherein said cargo is hydrophobic.
10. The method of claim 9 , wherein said hydrophobic cargo is inside the lipid bilayer.
11. The method of claim 1 , wherein the cargo-loaded pHLIP+ liposome comprises non-pore forming pHLIP polypeptides covalently attached to a phospholipid in the lipid bilayer of said liposome.
12. The method of claim 1 , wherein said target cell is in tissue affected by cancer, inflammation, ischemia, stroke, arthritis, infection with a microorganism, or atherosclerotic plaques.
13. The method of claim 1 , wherein said pHLIP+ liposome preferentially fuses with a membrane of a lysosomal compartment of said target cell after uptake by endocytosis.