Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells

To establish a potential gene-delivery system with the ability to deliver plasmid DNA to dendritic cells (DCs) more efficiently and specifically, we designed and synthesized a low-molecular-weight polyethyleneimine and triethyleneglycol polymer (PEI-TEG) and a series of its mannosylated derivatives.

PEI-TEG was synthesized from PEI2000 and PEI600 with TEG as the cross-linker. PEI-TEG was then linked to mannose via a phenylisothiocyanate bridge to obtain man-PEI-TEG conjugates. The DNA conveyance abilities of PEI-TEG, man-PEI-TEG, as well as control PEI25k were evaluated by measuring their zeta potential, particle size, and DNA-binding abilities. The in vitro cytotoxicity, cell uptake, and transfection efficiency of these PEI/DNA complexes were examined on the DC2.4 cell line. Finally, a maturation experiment evaluated the effect of costimulatory molecules CD40, CD80, and CD86 on murine bone marrow-derived DCs (BMDCs) using flow cytometry.

PEI-TEG and man-PEI-TEG were successfully synthesized and were shown to retain the excellent properties of PEI25k for condensing DNA. Compared with PEI-TEG as well as PEI25k, the man-PEI-TEG had less cytotoxicity and performed better in both cellular uptake and transfection assays in vitro. The results of the maturation experiment showed that all the PEI/DNA complexes induced an adequate upregulation of surface markers for DC maturation.

These results demonstrated that man-PEI-TEG can be employed as a DC-targeting gene-delivery system.