Formation and characterization of DNA-polymer-condensates based on poly(2-methyl-2-oxazoline) grafted poly(L-lysine) for non-viral delivery of therapeutic DNA

[摘要]：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. PLL(20)g(7)PMOXA(4) 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 similar to 100 nm and were found to be stable in serum and after 70 degrees 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, PLL(20)g(7)PMOXA(4) copolymers might be promising as alternative to PLL-g-PEG-DNA condensates for delivery of therapeutic DNA. (C) 2011 Elsevier Ltd. All rights reserved.

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