Formation of polyamidine-chromophore and polyamidine-(chromophore-poly(propylene oxide)-chromophore) complexes in methanol

Savitsky, A. O.; Gasilova, Ekaterina R.; Теньковцев, А. В.

doi:10.1134/s0965545x09030043

Cited by 2 publications

(1 citation statement)

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“…We hypothesized that incorporation of ortho esters to the polymer main-chains would facilitate efficient gene delivery via enhanced endosomal escape of complex and release of DNA. Hydrolysis of ortho esters in the mildly acidic endosomes would increase osmotic pressure and swelling of the carriers, which is expected to help to supplement the poor buffering capacity of polyamidines due to their pKa values as high as about 11 [32] and to efficiently unpack nucleic acids due to the dissociation of copolymer vectors. Here we report the synthesis of the new polyamidine-based copolymers, poly(ortho ester amidines) (POEAmd), and the results of physico-chemical characterization of copolymer/DNA plasmid polyplexes, including pH-triggered DNA release.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of new poly(ortho ester amidine) copolymers for non-viral gene delivery

Tang

Wang

2011

Polymer

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A new type of pH-labile cationic polymers, poly(ortho ester amidine) (POEAmd) copolymers, has been synthesized and characterized with potential future application as gene delivery carriers. The acid-labile POEAmd copolymer was synthesized by polycondensation of a new ortho ester diamine monomer with dimethylaliphatimidates, and a non-acid-labile polyamidine (PAmd) copolymer was also synthesized for comparison using a triethylene glycol diamine monomer. Both copolymers were easily dissolved in water, and can efficiently bind and condense plasmid DNA at neutral pH, forming nano-scale polyplexes. The physico-chemical properties of the polyplexes have been studied using dynamic light scattering, gel electrophoresis, ethidium bromide exclusion, and heparin competition. The average size of the polyplexes was dependent on the amidine: phosphate (N:P) ratio of the polymers to DNA. Polyplexes containing the acid-labile POEAmd or the non-acid-labile PAmd showed similar average particle size, comparable strength of condensing DNA, and resistance to electrostatic destabilization. They also share similar metabolic toxicity to cells as measured by MTT assay. Importantly, the acid-labile polyplexes undergo accelerated polymer degradation at mildly-acid-pHs, resulting in increasing particle size and the release of intact DNA plasmid. Polyplexes from both types of polyamidines caused distinct changes in the scattering properties of Baby Hamster Kidney (BHK-21) cells, showing swelling and increasing intracellular granularity. These cellular responses are uniquely different from other cationic polymers such as polyethylenimine and point to stress-related mechanisms specific to the polyamidines. Gene transfection of BHK-21 cells was evaluated by flow cytometry. The positive yet modest transfection efficiency by the polyamidines (acid-labile and non-acid-labile alike) underscores the importance of balancing polymer degradation and DNA release with endosomal escape. Insights gained from studying such acid-labile polyamidine-based DNA carriers and their interaction with cells may contribute to improved design of practically useful gene delivery systems.

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Section: Introductionmentioning

confidence: 99%