کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7366 | 550 | 2011 | 13 صفحه PDF | دانلود رایگان |
Successful gene delivery systems deliver DNA in a controlled manner combined with minimal toxicity and high transfection efficiency. Here we investigated 15 different copolymers of poly(l-lysine)-graft-poly(2-methyl-2-oxazoline) (PLL-g-PMOXA) of variable grafting densities and PMOXA molecular weights for their potential to complex and deliver plasmid DNA. PLL20g7PMOXA4 formed at N/P charge ratio of 3.125 was found to transfect 9 ± 1.6% of COS-7 cells without impairment of cell viability. Furthermore these PLL-g-PMOXA-DNA condensates were internalized 2 h after transfection and localized in the perinuclear region after 6 h. The condensates displayed a hydrodynamic diameter of ∼100 nm and were found to be stable in serum and after 70 °C heat treatment, moreover the condensates protected DNA against DNase-I digestion. The findings suggest that DNA-PMOXA-g-PLL condensate formation for efficient DNA-delivery strongly depends on PMOXA grafting density and molecular weight showing an optimum at low grafting density between 7 and 14% and medium N/P charge ratio (3.125–6.25). Thus, PLL20g7PMOXA4 copolymers might be promising as alternative to PLL-g-PEG-DNA condensates for delivery of therapeutic DNA.
Journal: Biomaterials - Volume 32, Issue 22, August 2011, Pages 5291–5303