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آکتا بیومتریال
جزئیات رویداد
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  • influence of the polyanion on the physico-chemical properties and biological activities of polyanion/dna/polycation ternary polyplexes

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    • تاریخ ارائه: 1392/01/01
    • تاریخ انتشار در تی پی بین: 1392/01/01
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     it was recently reported that polyanion/dna/polycation ternary polyplexes markedly improve gene transfection activity in comparison with the original dna/polycation binary polyplexes. in this study to explore the influence of the polyanion on the physico-chemical properties and biological activity of polyanion/pdna/polycation ternary polyplexes four types of biocompatible polyanions were selected, mainly based on the acid strength of the anionic functional groups and the molecular rigidity on forming ternary polyplexes with 25 kda polyethyleneimine and dna. polyanion loosening of the dna polyplex, weakening of the adsorption of serum proteins and improving of cellular uptake, which are thought to be important factors leading to a high transfection efficiency of dna ternary polyplexes, were specifically investigated. electrophoresis retardation analysis indicated that the loosening capacity of polyanions depended on the pka value of the functional anion groups as well as the flexibility of the polyanion. the low pka and flexible structure of the polyanions tended to loosen the compact dna polyplexes. thermodynamic analysis by isothermal titration calorimetry provided direct evidence about the serum protein–dna ternary polyplex interactions. the polyanion/pdna/polycation ternary polyplexes exhibited obviously lower binding affinities and less adsorption to serum proteins compared with the original dna/polycation binary polyplexes. these relatively stable dna ternary polyplexes maintained high levels of cellular uptake and intracellular accumulation in serum-containing medium that correlated with their high transfection efficiency. in contrast, the original pdna/polycation binary polyplexes became clustered by strong adsorption of large amounts of serum proteins, leading to a sharp reduction in cellular uptake and intracellular accumulation, and thus low gene transfer efficiency. these results provide a basis for the development of polyanion/dna/polycation ternary polyplexes for polyfection.

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