Abstract
Surface modification by poly(ethylene glycol) (PEG) onto gene carrier prepared through the electrostatic assembly of pDNA and polycation (polyplex) is a widely acknowledged strategy to advance their systemic application. In this regard, PEG crowdedness on the polyplex surface should give important contribution in determining blood circulation property; however its accurate quantification has never been demonstrated. We report here the first successful determination of PEG crowdedness for PEGylated polyplexes (polyplex micelle) formed from PEG–poly(l-lysine) block copolymers (PEG–PLys) and plasmid DNA (pDNA). Tethered PEG chains were found to adopt mushroom and even squeezed conformation by modulating PEG crowdedness through PLys segment length. Energetic analysis was conducted on the polyplex micelle to elucidate effect of PEG crowdedness on shape and clarify its essential role in regulating packaging structure of pDNA within the polyplex micelle. Furthermore, the PEG crowdedness significantly correlated ...
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