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Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells

Authors Sun X, Chen S, Han J, Zhang Z

Received 13 March 2012

Accepted for publication 5 April 2012

Published 14 June 2012 Volume 2012:7 Pages 2929—2942

DOI https://doi.org/10.2147/IJN.S31760

Review by Single-blind

Peer reviewer comments 3

Xun Sun, Simu Chen, Jianfeng Han, Zhirong Zhang

Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China

Background: 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.
Methods: 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.
Results: 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.
Conclusion: These results demonstrated that man-PEI–TEG can be employed as a DC-targeting gene-delivery system.

Keywords: dendritic cells, DCs, mannose, polyethyleneimine, PEI, gene delivery

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