Hyperbranched dendron and methods of synthesis and use thereof
First Claim
1. A polymer comprising:
- a surface defined by the polymer;
a branched polyethyleneimine (B-PEI) core within the surface;
a plurality of primary amine groups at the surface; and
a plurality of secondary and tertiary amine groups positioned at the core;
wherein the polymer is a flexible hyperbranched dendron polymer.
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Abstract
Hyperbranched dendron (HD) polymers are synthesized using low molecular weight polyethyleneimine (BPEI-L) as a core and used for gene delivery. The obtained polymers display low toxicity and efficient gene delivery at low nitrogen-to-phosphate (N/P) ratios. Using successive attachment of ethyleneimine moieties to a PEI core, the polymer has a lower relative ratio of linear-to-branched structures than in the core PEI. The more extensive branching enables the polymer to condense plasmid DNA into nanostructure complexes with a size of less than or equal to about 100 nm. The complexes are stable and efficient in transfecting cells in the presence of serum. Bioluminescent imaging of in vivo gene expression using a luciferase reporter gene performed in live mice showed gene expression in the liver and in submandibular lymph nodes.
27 Citations
32 Claims
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1. A polymer comprising:
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a surface defined by the polymer; a branched polyethyleneimine (B-PEI) core within the surface; a plurality of primary amine groups at the surface; and a plurality of secondary and tertiary amine groups positioned at the core; wherein the polymer is a flexible hyperbranched dendron polymer. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 28)
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- 11. A hyperbranched dendron polymer having a randomly branched structure, a molecular weight of about 10 to 25 kD, and a ratio of secondary to tertiary amine groups of less than or equal to about 1.5 to 1.
- 20. A hyperbranched dendron polymer made by a process comprising iterative attachment of ethyleneimine moieties to a branched polyethyleneimine core, wherein the process increases the amount of secondary and tertiary amines in the polymer while maintaining a plurality of primary amines on a surface of the polymer.
Specification