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.

What is claimed is: 
     
         1 . A composition for delivery of an active agent to cells or tissues comprising a wholly or partially double-stranded synthetic DNA carrier, an active agent intercalated in double-stranded portions of the DNA carrier, and a targeting agent linked to the DNA carrier, wherein the targeting agent is selected from the group consisting of
 a) an antibody or peptide that binds to the transferrin receptor, and   b) an antibody or peptide that binds to G8 antigen.   
     
     
         2 . The composition of  claim 1 , wherein the active agent is intercalated in the double stranded DNA through hydrogen bonding. 
     
     
         3 . The composition of  claim 1  wherein the DNA dendrimer comprises 3-216 hybridized single strands of DNA. 
     
     
         4 . 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. 
     
     
         5 . The composition of  claim 4 , wherein the active agent is berberine, an acridine, daunomycin, doxorubicin, daunorubicin, dactinomycin, cisplatin, carboplatin or thalidomide. 
     
     
         6 . A pharmaceutical composition comprising the composition of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the targeting agent is an antibody that binds to G8 antigen. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the targeting agent is a monoclonal antibody that binds to G8 antigen and the active agent is doxorubicin. 
     
     
         9 . The pharmaceutical composition of  claim 6 , wherein the targeting agent is a peptide that binds to transferrin receptor. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the active agent is doxorubicin. 
     
     
         11 . A method of making the composition of  claim 1 , comprising assembling single-stranded DNA oligonucleotides to form wholly or partially double-stranded DNA, linking the 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. 
     
     
         12 . The method of  claim 11 , wherein the single-stranded DNA oligonucleotides are assembled simultaneously with contacting the wholly or partially double-stranded DNA with the active agent. 
     
     
         13 . The method of  claim 11 , wherein the wholly or partially double-stranded DNA is contacted with the active agent after assembly. 
     
     
         14 . The method of  claim 13 , further comprising linking the targeting agent to the wholly or partially double-stranded DNA before contacting with the active agent. 
     
     
         15 . A method of delivering an active agent to a cell or tissue comprising contacting the cell or tissue with the pharmaceutical composition of  claim 6 . 
     
     
         16 . A method of treating a disease or condition in a patient comprising administering to the patient the pharmaceutical composition of  claim 6 . 
     
     
         17 . The method of  claim 16 , wherein the targeting agent is an antibody or peptide that binds to G8 antigen, and the pharmaceutical composition is administered for prevention of posterior capsular opacification or for reducing the incidence of posterior capsular opacification. 
     
     
         18 . The method of  claim 17 , wherein the targeting agent is a monoclonal antibody that binds to G8 antigen and the active agent is doxorubicin. 
     
     
         19 . The method of  claim 16 , wherein the targeting agent is an antibody or peptide that binds to the transferrin receptor, and the pharmaceutical composition is administered for depletion of pancreatic tumor cells. 
     
     
         20 . The method of  claim 19 , wherein the targeting agent is a peptide that binds to the transferrin receptor and the active agent is doxorubicin.