Bioinspired phosphorylcholine-modified polyplexes as an effective strategy for selective uptake and transfection of cancer cells

• Phosphorylcholine modification improved colloid stability and reduced cytotoxicity.
• Bioinspired polyplexes were selectively uptaked by liver cancer cells.
• Phosphorylcholine-modified polyplexes showed high transfection in cancer cells.

We demonstrated here that the phosphorylcholine-modified polyplexes can be explored as effective gene vector for selective uptake and high transfection of cancer cells. 12-acryloyloxy dodecyl phosphorylcholine modified polyethyleneimine (PEI–ADPC) with grafting level about 13%, 8.3% and 4.5% was successfully synthesized. Gel retardation assay indicated that ADPC modification did not affect the DNA condensation ability. The PEI–ADPC13%/DNA and PEI–ADPC8.3%/DNA polyplexes were under 100 nm with a beneficial neutral surface at N/P ratio of 30. Sufficient ADPC shell endowed the polyplexes with high colloidal stability and low cytotoxicity. Compared to PEGylated polyplexes, it was interesting to find out that the PEI–ADPC/DNA polyplexes were selectively uptaked by liver cancer HepG2 cells. At the presence of chloroquine to exclude the limitation of lysosome escape, the ADPC-modified polyplexes showed more effective gene transfection in cancer cells than in normal cells because of the selective cell uptake. In conclusion, the convenient PC-modification modality was found to have both the function of biostability in the physiological environment and targetability toward cancer cells uniquely, which might have great potential use in cancer gene therapy.

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