Compositions and methods for polymer-caged liposomes

Abstract

The present invention provides liposomal compositions and methods of using such compositions in vitro and in vivo. In particular, the present invention provides stable, polymer-caged liposomes comprising a pH responsive delivery mechanism for delivery of nucleic acids, peptides, small molecules, drugs, etc. in vitro and in vivo.

We claim: 
     
         1 . A composition comprising a pH-responsive stable polymer-caged liposome. 
     
     
         2 . The composition of  claim 1 , wherein said liposome is a pH-responsive delivery system for payloads. 
     
     
         3 . The composition of  claim 2 , wherein said liposome comprises a payload selected from the group consisting of: a drug , a small molecule, an inorganic solid, a polymer, a biopolymer, a nucleic acid, and a peptide. 
     
     
         4 . The composition of  claim 1 , wherein said pH-responsive stable polymer-caged liposome comprises a membrane-anchoring group. 
     
     
         5 . The composition of  claim 4 , further comprising a linker, wherein said anchoring group is attached to said linker. 
     
     
         6 . The composition of  claim 4 , further comprising a targeting ligand, wherein said targeting ligand is operably connected to said membrane-anchoring group. 
     
     
         7 . The composition of  claim 4 , further comprising a detectable molecule, wherein said detectable molecule is operably connected to said membrane-anchoring group. 
     
     
         8 . The composition of  claim 4 , further comprising a drug molecule, wherein said drug molecule is operably connected to said membrane-anchoring group. 
     
     
         9 . The composition of  claim 2 , wherein said membrane-anchoring group comprises cholesterol-terminated poly(acrylic acid). 
     
     
         10 . A method for transfecting cells comprising:
 a) providing:
 i.) a pH-responsive, stable polymer-caged liposome , 
 ii) a eukaryotic cell, 
 iii) an agent selected from the group consisting of: a nucleic acid, a peptide, a small molecule, a drug, an inorganic solid, a polymer, or a biopolymer; 
   b) complexing said liposome with said agent thereby forming a liposome carrying a payload that comprises said agent; and,   c) transfecting said liposome into said eukaryotic cell such that release of the payload is realized at a particular pH.   
     
     
         11 . The method of  claim 10 , wherein said transfecting is performed in vitro in mammalian cells. 
     
     
         12 . The method of  claim 10 , wherein said transfecting is performed in vivo in a subject. 
     
     
         13 . A delivery system comprising a bare liposome, a membrane-anchoring group attached to a crosslinkable polymer, and a bifunctional crosslinking molecule that crosslinks with the crosslinkable polymer, wherein said delivery system delivers a payload to a cell. 
     
     
         14 . The delivery system of  claim 13 , wherein said delivery system is further pH-responsive such that said payload is delivered to said cell based on the pH in said cell. 
     
     
         15 . The delivery system of  claim 13 , wherein said payload is from the group consisting of small molecules, nucleic acids, drugs, inorganic solids, polymers, biopolymers, peptides, or proteins. 
     
     
         16 . The delivery system of  claim 13 , wherein said liposome comprises a payload selected from the group consisting of: a drug, small molecule, inorganic solid, polymers, biopolymers, a nucleic acid, and a peptide. 
     
     
         17 . The delivery system of  claim 13 , further comprising a targeting ligand, wherein said targeting ligand is operably connected to either said bifunctional crosslinking molecule or said membrane-anchoring group. 
     
     
         18 . The delivery system of  claim 13 , further comprising a detectable entity, wherein said detectable entity is operably connected to either said bifunctional crosslinking molecule or said membrane anchoring group. 
     
     
         19 . The delivery system of  claim 13 , further comprising a drug molecule, wherein said drug molecule is operably connected to either said bifunctional crosslinking molecule or said membrane anchoring group.