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Polydepsipeptide Block Stabilized Polyplexes For Efficient Transfection of Primary Human Cells

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ACS Editors choice. Source: ACS

Degradable block copolymers have shown great potential to combine transfection capability with low toxicity of the transfection agent. We selected pure oligodepsipeptides as a hydrophobic block in order to achieve strong physical interactions by a strictly alternating sequence structure of isoleucine and glycolide repeating units. Incorporated in a di- or triblock copolymer architecture this segment guides the assembly of carriers and DNA-polymer polyplexes as well as the often inefficient steps of intracellular trafficking that can be directly influenced by the nanoparticle architecture: the evasion of the polyplex from the endosome and its concomitant disintegration, releasing the DNA in the cytoplasm before it would otherwise be degraded in the lysosome.

Especially the high transfection efficacy of the block copolymer carriers for primary cells is noteworthy. The latter could be explained by an effective endosomal escape, as microscopically observed, and free DNA could be localized in the cell nucleus to initiate gene expression. In this way, the introduced polymers outperformed established transfection agents such as lipofectamine on several levels.

These results were just published in Biomacromolecules.

Read Publication online in Biomacromolecules