Citation: Bo Zhang, Xin-peng M, Mei-hua Sui, Edward Van Kirk, William J. Murdoch, Maciej Radosz, Neng-ming Lin, You-qing Shen. Guanidinoamidized Linear Polyethyleneimine for Gene Delivery[J]. Chinese Journal of Polymer Science, ;2015, 33(6): 908-919. doi: 10.1007/s10118-015-1644-9 shu

Guanidinoamidized Linear Polyethyleneimine for Gene Delivery

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1. Institute for Individualized Medicine, Hangzhou First People's Hospital, Hangzhou 310006, China
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2. Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, China
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3. Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming 82071, USA
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Center for Bionanoengineering and the State Key Laboratory for Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China
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Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071, USA
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Institute for Individualized Medicine, Hangzhou First People's Hospital, Hangzhou 310006, China

Received Date: 22 October 2014
Revised Date: 12 November 2014

Fund Project: This work was financially supported by the Qianjiang Talent Program of Zhejiang Province (2014.1-2015.12, Zhang Bo), the National Natural Science Fund for Distinguished Young Scholars (No. 50888001), the National Natural Science Foundation of China (No. 20974096) , Zhejiang Provicial Program for the Cultivation of High-level Innovative Health Talents (2010-190-4), and the U.S. National Science Foundation (No. CBET 0753109, DMR-0705298) and Department of Defense (No. BC083821).

Guanidine was introduced to low molecular weight linear polyethyleneimine (LPEI) via amide groups, to explore the effect of both guanidine degree and pendant chain length on its transfection behavior. The resulting guanidinoamidized LPEIs (GLPEIs) could dramatically reduce LPEI's toxicity, enhance its DNA-packaging capability, cellular uptake and therefore transfection efficiency. These polyplexes were taken up very efficiently via caveolae-mediated endocytosis and their transfection efficiencies in ovarian cancer cells were significantly improved compared to native LPEI10k polyplexes. Among these GLPEIs, LPEI-C3-G100 showed higher DNA affinity even than LPEI25k and the highest transfection efficiency, probably due to the optimization of polymer chain flexibility. Of notice, LPEI-C3-G100 polyplexes could more effectively accumulate into cytoplasm than LPEI25k, although the transfection efficiency of LPEI-C3-G100 polyplexes was not superior to that of LPEI25k polyplexes, which would be probably attributed to the more efficient release of LPEI25k polyplexes than LPEI-C3-G100 polyplexes in the cytoplasm.
- Polyethyleneimine,
- Guanidine,
- Gene delivery,
- Cellular uptake
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