Targeted carriers for intracellular drug delivery
View Patent ↗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 dendrimer,
a cargo which is a biologically active agent whose action is required in the cytosol or other intracellular compartment which the cargo cannot access by itself,
and a targeting moiety which is a polypeptide which binds to a cell surface molecule,
wherein said composition provides cytosolic delivery of the cargo without the need for other means to permeate or disrupt the cell membrane.
2. The composition of claim 1 , wherein said targeting moiety is linked to said DNA dendrimer.
3. The composition of claim 1 , wherein said cargo is linked to said DNA dendrimer.
4. The composition of claim 1 , further comprising a secondary carrier linked to said DNA dendrimer, wherein the secondary carrier is polyethylene glycol (PEG).
5. The composition of claim 4 , wherein said targeting moiety is linked to said secondary carrier.
6. The composition of claim 1 , wherein said cell surface molecule is selected from the group consisting of intercellular adhesion molecule (ICAM), 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), selectins, mucosal vascular addressin cell adhesion molecule (MAdCAM), CD44, LFA2, LFA-3, basigin, mannose-6-phosphate receptor, and transferrin receptor.
7. A pharmaceutical composition comprising a composition of claim 1 and a pharmaceutically-acceptable excipient.
8. The composition of claim 1 , wherein said polypeptide is an antibody selected from the group consisting of a monoclonal antibody, a humanized antibody, a synthetic antibody, single chain variable fragment (scFV), 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.
9. A method for delivering a cargo to a cell, said method comprising contacting said cell with a composition of claim 1 wherein said targeting moiety binds said cell, thereby delivering the cargo to said cell.
10. The method of claim 9 , wherein said cargo is delivered to the cytosol or intracellular compartments of said cell.
11. The method of claim 9 , wherein said cell is a mammalian cell.
12. A composition comprising a DNA dendrimer, a polypeptide which binds to a cell surface molecule, a biologically active agent, and polyethylene glycol (PEG).
13. A pharmaceutical composition comprising a DNA dendrimer, a polypeptide which binds to a cell surface molecule, a biologically active agent and a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , further comprising polyethylene glycol (PEG).
15. A composition consisting essentially of
a DNA dendrimer,
a cargo which is a biologically active agent,
and a targeting moiety which is a polypeptide which binds to a cell surface molecule,
wherein said composition provides intracellular delivery of the cargo.