Tat-conjugated hyaluronic acid enveloping polyplexes with facilitated nuclear entry and improved transfection

The biocompatible envelop of virus gives us some inspiration in designing non-viral gene delivery system. In this research, Tat-conjugated hyaluronic acid with different grafting degree was synthesized. By coating HA-Tat to PEI/DNA complexes, the enveloping ternary polyplexes was successfully constructed due to the electrostatic interaction. At N/P/COOH ratio of 8:1:8, spherical nanoparticles were formed with diameter about 150–180 nm. Gel retardation assay indicated the disassembly did not occur. The stability of enveloping polyplexes in physiological condition was improved. HA-Tat envelop improved cell uptake of polyplexes. The intracellular distribution showed the ternary polyplexes could be able to efficiently release DNA and deliver DNA into the nuclei, resulted in higher transfection efficiency than PEI/DNA polyplexes. Thereby, the HA-Tat enveloping polyplexes with facilitated nuclear entry and improved transfection might have a promising application in non-viral gene therapy.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The stability of HA-Tat enveloping polyplexes was significantly improved. ► HA-Tat envelop improved cell uptake of polyplexes. ► The enveloping polyplexes facilitated nuclear entry and improved transfection.