Cellular Delivery of DNA Intercalating Agents
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.