DNA Polyplexes Formed Using PEGylated Biodegradable Hyperbranched Polymers

Abstract

A novel PEGylated biodegradable hyperbranched PEG-b-PDMAEMA has been synthesized. The low toxicity, small molecular weight PDMAEMA chains were crosslinked using a biodegradable disulfide-based dimethacrylate (DSDMA) agent to yield higher molecular weight hyperbranched polymers. PEG chains were linked onto the polymer surface, masking the positive charge (as shown by Zeta potential measurements) and reducing the toxicity of the polymer. The hyperbranched structures were also cleaved under reducing conditions and analyzed, confirming the expected component structures. The hyperbranched polymer was mixed with DNA and efficient binding was shown to occur through electrostatic interactions. The hyperbranched structures could be reduced easily, generating lower toxicity oligomer chains.

Light‐Switchable Polymer from Cationic to Zwitterionic Form: Synthesis, Characterization, and Interactions with DNA and Bacterial Cells

“…At and above this concentration, poly 1 retards DNA from electrophoretic separation. This amount of poly 1 capable of condensing dsDNA corresponds to about six polymeric chains per one dsDNA molecule (taking into account the number average molar mass of poly 1 determined by SEC using effective calibration to pullulans), which corresponds to previous observations 32, 33. Dynamic light scattering and zeta potential measurements for polyplex (entry v) between poly 1 and dsDNA showed an average diameter of 170 nm and a charge of +4 mV, respectively.…”

Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

“…152 Early work on application of these branched polymer systems to DNA delivery was established by the Davis group, who synthesised highly branched PDMAEMA-b-PEG using RAFT polymerisation. 159,160 The structures were formed with a redox sensitive divinyl comonomer, to yield high molecular weight polymers able to be cleaved into lower molecular weight polymer chains. Efficient binding of DNA was shown to occur through electrostatic interactions.…”

RAFT Polymerization and Thiol Chemistry: A Complementary Pairing for Implementing Modern Macromolecular Design

“…For instance, the copolymerization of dimethylaminoethyl acrylate (DMAEA) and a biodegradable disulfide based dimethacrylate reagent has been exploited to synthesize cationic hyperbranched polymers for DNA delivery. [165] The ''core first approach'' to star polymers requires a multi-functional initiator, yielding stars with constant and pre-determined arm numbers. [166] Liu et al synthesized three armed stars containing biodegradable disulfides via covalent attachment of a trithiocarbonate RAFT agent, 3-[pyridyldisulfide]-ethyl, 3-benzyltrithiocarbonate propionate to a trithiol precursor, trimethylolpropane tris [3-mercaptopropionate] through disulfide coupling via Z-groups, followed by direct chain propagation from the RAFT cores to afford three-armed star polymers.…”