Targeted carriers for intracellular drug delivery

Abstract

The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.

1 . A composition comprising a DNA-based carrier and a targeting moiety. 
     
     
         2 . The composition of  claim 1 , wherein said targeting moiety is linked to said DNA-based carrier. 
     
     
         3 . The composition of  claim 1 , further comprising a cargo selected from a biologically active agent, a therapeutic agent, an imaging agent, a monitoring agent and combinations thereof. 
     
     
         4 . The composition of  claim 3 , wherein said cargo is linked to said DNA-based carrier. 
     
     
         5 . The composition of  claim 1 , wherein the DNA-based carrier is selected from a DNA dendrimer, a double-stranded DNA, a single-stranded DNA, a single-stranded hairpin DNA and multimers thereof. 
     
     
         6 . The composition of  claim 1 , wherein said DNA-based carrier is a DNA dendrimer, said composition further comprises a cargo which is RNA. 
     
     
         7 . The composition of  claim 1 , further comprising a secondary carrier selected from a liposome, a non-DNA dendrimer, a polymer carrier, a microbubble, a paramagnetic particle, a ferromagnetic particle, a self-assembled polymer, a polymersome, a filomicelle, a protein or lipoprotein particle, and a cellular component. 
     
     
         8 . The composition of  claim 7 , wherein said targeting moiety is linked to said secondary carrier. 
     
     
         9 . The composition of  claim 1 , wherein said targeting moiety associates with at least one cell component comprising of a cellular protein, carbohydrate, nucleic acid, lipid or combination thereof. 
     
     
         10 . The composition of  claim 9 , wherein said targeting moiety associates with a cellular component associated with intracellular, intercellular or trans-cellular transport. 
     
     
         11 . The composition of  claim 10 , wherein said cellular component is a cellular adhesion molecule (CAM), selected from ICAM-1, platelet-endothelial cell adhesion molecule (PECAM), PECAM-1, activated leukocyte cell adhesion molecule (ALCAM), B-35 lymphocyte cell adhesion molecule (BL-CAM), vascular cell adhesion molecule (VCAM), mucosal vascular addressin cell adhesion molecule (MAdCAM), CD44, LFA2, LFA-3, and basigin. 
     
     
         12 . The composition of  claim 10 , wherein said cellular component is selected from mannose-6-phosphate receptor and transferrin receptor. 
     
     
         13 . The composition of  claim 1 , wherein said targeting moiety is selected from the group consisting of a protein, an antibody, an aptamer, a nucleic acid, a peptide, a carbohydrate, a lipid, a vitamin, a toxin, a component of a microorganism, a hormone, a receptor ligand and any derivative thereof. 
     
     
         14 . The composition of  claim 13 , wherein said antibody is selected from a monoclonal antibody, a humanized antibody, a synthetic antibody, a heavy chain antibody, and a biologically active fragment of an antibody, wherein the biologically active fragment is a Fab fragment, a F(ab′)2 fragment, and a Fv fragment. 
     
     
         15 . The composition of  claim 14 , wherein said antibody is an anti-ICAM-1 antibody, an anti-PECAM-1 antibody, an anti-transferrin receptor antibody or an antimannose-6-phosphate receptor antibody. 
     
     
         16 . A pharmaceutical composition comprising a composition of  claim 1  and a pharmaceutically-acceptable excipient. 
     
     
         17 . A method for delivering a cargo to a cell, said method comprising contacting said cell with a DNA-based carrier and said cargo, wherein said DNA-based carrier comprises a targeting moiety, wherein said targeting moiety binds said cell, thereby delivering the cargo to said cell. 
     
     
         18 . The method of  claim 17 , wherein said cargo is delivered to the cytosol of said cell. 
     
     
         19 . The method of  claim 17 , wherein said cell is a mammalian cell, and wherein said targeting moiety associates with at least one of a cellular protein, carbohydrate, or lipid or combination thereof on the cell. 
     
     
         20 . The method of  claim 17 , wherein said cargo is RNA.