Abstract

Conventionally, cationic polymers can deliver genome-editing macromolecules into target cells via endocytosis. However, these vectors have low targeting ability and highly undesirable endosome trapping, and hence, only a very small fraction of delivered molecules can enter the cytosol of target cells, while most of them are degraded in lysosomes. Up to date, both targeting and bypassing endosomal trapping delivery are still challenging. It is very intersting to find that dipicolylamine-zinc (DPA-Zn) structures on polyplex surfaces can enable polyplexes to directly transport genome editing molecules into the cytosol without severe endosomal trapping not via classical endocytic pathways but via a new phosphatidylserine-mediated endocytic pathway. Moreover, DPA-Zn can highly target tumors, which highly enhances gene editing efficiency. This method provides an innovative method for successful targeting and bypassing endosomal trapping delivery of different biomacromolecules into cancer cells, bypassing the major obstacle of endosomal trapping.

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