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 LPEI

10k

polyplexes. Among these GLPEIs

LPEI-C

3

-G

100

showed higher DNA affinity even than LPEI

25k

and the highest transfection efficiency

probably due to the optimization of polymer chain flexibility. Of notice

LPEI-C

3

-G

100

polyplexes could more effectively accumulate into cytoplasm than LPEI

25k

although the transfection efficiency of LPEI-C

3

-G

100

polyplexes was not superior to that of LPEI

25k

polyplexes

which would be probably attributed to the more efficient release of LPEI

25k

polyplexes than LPEI-C

3

-G

100

polyplexes in the cytoplasm.