Multi-arm biodegradable polymers for nucleic acid delivery
In some embodiments, the present disclosure pertains to compositions for nucleic acid delivery into cells. In some embodiments, the composition comprises: (1) a cationic polymer unit comprising a plurality of polymeric arms, where the plurality of polymeric arms comprise poly(aspartic acid) derivatives; and (2) a nucleic acid associated with the cationic polymer unit. In some embodiments, the cationic polymer unit comprises a linker covalently associated with the plurality of polymeric arms. In some embodiments, the cationic polymer unit has a dendritic shape. In some embodiments, the cationic polymer unit has a star-like shape. In some embodiments, the cationic polymer unit is biodegradable. Further embodiments of the present disclosure pertain to methods of delivering a nucleic acid into cells by introducing into the cells one or more of the compositions of the present disclosure.
1. A composition for nucleic acid delivery into cells, wherein the composition comprises:
a cationic polymer unit comprising a linker and a plurality of polymeric arms associated with the linker,
wherein the plurality of polymeric arms comprise at least about 8 polymeric arms,
wherein the plurality of polymeric arms comprise poly(aspartic acid) derivatives, and
wherein the polymeric arms are branched from the linker to form a dendritic shape; and
a nucleic acid associated with the cationic polymer unit.
2. The composition of claim 1 , wherein the linker is covalently associated with the plurality of polymeric arms.
3. The composition of claim 1 , wherein the linker is selected from the group consisting of small molecules, macromolecules, nanoparticles and combinations thereof.
4. The composition of claim 1 , wherein the poly(aspartic acid) derivatives comprise from about 2 units to about 500 units of aspartic acid derivatives.
5. The composition of claim 1 , wherein the poly(aspartic acid) derivatives comprise amine-modified aspartic acid derivatives (amine-modified poly(aspartic acid)).
6. The composition of claim 1 , wherein the poly(aspartic acid) derivatives comprise diethylenetriamine-modified aspartic acid derivatives (PAsp(DET) n ).
7. The composition of claim 6 , wherein n is an integer ranging from about 2 to about 500.
8. The composition of claim 1 , wherein the poly(aspartic acid) derivatives are selected from the group consisting of amine-modified poly(aspartic acid), (PAsp(DET) n ), where n ranges from about 2 to about 500, PAsp(DET) 100 , PAsp(DET) 70 , PAsp(DET) 200 , and combinations thereof.
9. The composition of claim 1 , wherein the plurality of polymeric arms comprise about 8 branches of PAsp(DET) 30 (8-arm PAsp(DET) 30 ).
10. The composition of claim 1 , wherein the cationic polymer unit is biodegradable.
11. The composition of claim 1 , wherein the nucleic acid is selected from the group consisting of DNA, RNA, siRNA, shRNA, miRNA, analogues thereof, and combinations thereof.
12. The composition of claim 1 , wherein the nucleic acid comprises plasmid DNA.
13. The composition of claim 1 , wherein the nucleic acid comprises a gene.
14. The composition of claim 1 , wherein the nucleic acid is associated with the cationic polymer unit through electrostatic interactions.
15. The composition of claim 1 , wherein the composition has an N/P ratio from about 1 to about 40.
16. A method of delivering a nucleic acid into cells, wherein the method comprises introducing into the cells a composition comprising:
a cationic polymer unit comprising a linker and a plurality of polymeric arms associated with the linker,
wherein the plurality of polymeric arms comprise at least about 8 polymeric arms,
wherein the plurality of polymeric arms comprise poly(aspartic acid) derivatives, and
wherein the polymeric arms are branched from the linker to form a dendritic shape; and
a nucleic acid associated with the cationic polymer unit.
17. The method of claim 16 , wherein the poly(aspartic acid) derivatives are selected from the group consisting of amine-modified poly(aspartic acid), (PAsp(DET) n ), where n ranges from about 2 to about 500, PAsp(DET) 100 , PAsp(DET) 70 , PAsp(DET) 200 , and combinations thereof.
18. The method of claim 16 , wherein the plurality of polymeric arms comprise about 8 branches of PAsp(DET) 30 (8-arm PAsp(DET) 30 ).
19. The method of claim 16 , wherein the cationic polymer unit is biodegradable.
20. The method of claim 16 , wherein the nucleic acid is selected from the group consisting of DNA, RNA, siRNA, shRNA, miRNA, analogues thereof, and combinations thereof.
21. The method of claim 16 , wherein the nucleic acid comprises plasmid DNA.
22. The method of claim 16 , wherein the nucleic acid comprises a gene.
23. The method of claim 16 , wherein the nucleic acid is associated with the cationic polymer unit through electrostatic interactions.
24. The method of claim 16 , wherein the composition has an N/P ratio from about 1 to about 40.
25. The method of claim 16 , wherein the method occurs in vivo in a subject.
26. The method of claim 25 , wherein the subject is a human being.
27. The method of claim 25 , wherein the composition is introduced into the cells of the subject by a method selected from the group consisting of oral administration (including gavage), inhalation, subcutaneous administration (sub-q), intravenous administration (I.V.), intraperitoneal administration (I.P.), intramuscular administration (I.M.), intrathecal injection, intratracheal injection, ocular injection, intradermal injection, intracardiac injection, intrathoracic injection, intracerebral injection, and combinations thereof.
28. The method of claim 16 , wherein the method occurs in vitro.
29. The method of claim 16 , wherein the composition is introduced into cells in vitro by transfection.