期刊
MACROMOLECULES
卷 46, 期 16, 页码 6585-6592出版社
AMER CHEMICAL SOC
DOI: 10.1021/ma401093z
关键词
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资金
- Core Research Program for Evolutional Science and Technology (CREST)
- Precursory Research for Embryonic Science and Technology (PRESTO) in Molecular Technology and Creation of New Functions from the Japan Science and Technology Corporation (JST)
- Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)
- Core-to-core Program, A. Advanced Research Networks
- Ministry of Education, Science, Sports and Culture, Japan (MEXT)
- Grants-in-Aid for Scientific Research [24790530, 25882011, 25000006] Funding Source: KAKEN
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 polypexes (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 to blood retention profile, approving its critical role on both shape and systemic circulation property.
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