Cellular Delivery of DNA Intercalating Agents

Abstract

Compositions and methods for targeted delivery of active agents to cells are provided. The compositions comprise a wholly or partially double-stranded synthetic DNA carrier, and an active agent intercalated in double-stranded portions of the DNA carrier. The DNA carrier may also be linked to a targeting agent. The compositions are useful for delivering an active agent into a targeted cell type, for example a cytotoxic agent.

1 . A composition for delivery of an active agent to cells or tissues comprising a wholly or partially double-stranded synthetic DNA carrier, and an active agent intercalated in double-stranded portions of the DNA carrier. 
     
     
         2 . The composition of  claim 1  further comprising a targeting agent linked to the DNA carrier. 
     
     
         3 . The composition of  claim 1 , wherein the double stranded DNA is greater than 5 base pairs long. 
     
     
         4 . The composition of  claim 1 , wherein the active agent is intercalated in the double stranded DNA through hydrogen bonding. 
     
     
         5 . The composition of  claim 2 , wherein the targeting agent is an antibody that binds to a cell surface protein, a peptide that binds to a cell surface protein or a ligand that binds to a cell surface receptor. 
     
     
         6 . The composition of  claim 5 , wherein the targeting agent is an antibody or peptide that binds to the transferrin receptor. 
     
     
         7 . The composition of  claim 5 , wherein the targeting agent is an antibody or peptide that binds to G8 antigen. 
     
     
         8 . The composition of  claim 1  comprising a targeting agent linked to a DNA dendrimer, wherein the active agent is intercalated in double-stranded portions of the DNA dendrimer. 
     
     
         9 . The composition of  claim 8  wherein the DNA dendrimer comprises 3-216 hybridized single strands of DNA. 
     
     
         10 . A The composition of  claim 1 , wherein the active agent is selected from the group consisting of chemotherapeutics, anti-infective agents, antimalarial agents, antiviral agents and antifungal agents. 
     
     
         11 . The composition of  claim 10 , wherein the active agent is berberine, an acridine, daunomycin, doxorubicin, daunorubicin, dactinomycin, cisplatin, carboplatin or thalidomide. 
     
     
         12 . The composition of  claim 8 , wherein the targeting agent is an antibody that binds to a cell surface protein, a peptide that binds to a cell surface protein or a ligand that binds to a cell surface receptor. 
     
     
         13 . The composition of  claim 12 , wherein the targeting agent is an antibody or peptide that binds to the transferrin receptor. 
     
     
         14 . The composition of  claim 12 , wherein the targeting agent is an antibody or peptide that binds to G8 antigen. 
     
     
         15 . A pharmaceutical composition comprising the composition of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         16 . A pharmaceutical composition comprising the composition of  claim 8  and a pharmaceutically acceptable excipient. 
     
     
         17 . A method of making a DNA carrier for delivery of an active agent to a cell or tissue comprising assembling single-stranded DNA oligonucleotides to form wholly or partially double-stranded DNA, linking a targeting agent to the wholly or partially double-stranded DNA, and contacting the wholly or partially double-stranded DNA with an active agent such that the active agent intercalates into double-stranded portions of the DNA. 
     
     
         18 .- 20 . (canceled) 
     
     
         21 . A method of delivering an active agent to a cell or tissue comprising contacting the cell or tissue with the pharmaceutical composition of  claim 16 . 
     
     
         22 . A method of treating a disease or condition in a patient comprising administering to the patient the pharmaceutical composition of  claim 16 . 
     
     
         23 .- 24 . (canceled) 
     
     
         25 . A composition for delivery of an active agent to cells or tissues comprising a wholly or partially double-stranded synthetic DNA dendrimer, a targeting agent linked to the DNA dendrimer, and an active agent intercalated in double-stranded portions of the DNA dendrimer;
 wherein the targeting agent is an antibody or peptide that binds to G8 antigen.