Tethered PEG Crowdedness Determining Shape and Blood Circulation Profile of Polyplex Micelle Gene Carriers

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• 作者：Theofilus A. Tockary ; Kensuke Osada ; Qixian Chen ; Kaori Machitani ; Anjaneyulu Dirisala ; Satoshi Uchida ; Takahiro Nomoto ; Kazuko Toh ; Yu Matsumoto ; Keiji Itaka ; Koji Nitta ; Kuniaki Nagayama ; Kazunori Kataoka
• 刊名：Macromolecules
• 出版年：2013
• 出版时间：August 27, 2013
• 年：2013
• 卷：46
• 期：16
• 页码：6585-6592
• 全文大小：411K
• 年卷期：v.46,no.16(August 27, 2013)
• ISSN：1520-5835

文摘

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鈥損oly(l-lysine) block copolymers (PEG鈥揚Lys) 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 to blood retention profile, approving its critical role on both shape and systemic circulation property.