2005 Fiscal Year Final Research Report Summary
Design for Novel Stimuli-Sensitive Hydrogel, Polysilamine, and its Materials Design
| Project/Area Number |
14350502
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
高分子構造・物性(含繊維)
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| Research Institution | UNIVERSITY OF TSUKUBA (2004-2005)
Tokyo University of Science (2002-2003) |
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Principal Investigator |
NAGASAKI Yukio UNIVERSITY OF TSUKUBA, Graduate School of Pure and Applied Sciences, professor, 大学院・数理物質科学研究科, 教授 (90198309)
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| Project Period (FY) |
2002 – 2005
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| Keywords | poly(silamine) / stimuli-sensitive hydrogel / rod-globule transition / Gene delivery / gene vector / DDS / intercellular trafficing |
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| Research Abstract |
Novel stimuli-sensitive poly(silamine), which consists of alternating 3-sila-3,3-dimethylpentamethylene and N,N'-diethyl-ethylenediamine, was designed. The poly(silamine) showed rod-globule transition by chaiging environmental pH change, viz., protonated poly(silamine) was hydrophilic and stiff extended conformation under low pH, while non-protonated poly(silamine) was flexsible hydrophobic material under high pH. Chemically crosslinked poly(silamine) gel showed an volume phase transition by pH change. When xerogel was soaked in acidic condition, the poly(silamine) gel swelled. At the same time, the network of the gel become stiff. This is striking contrast to other conventional hydrogel. Conventional gel becomes soft when it swells.
Using end functional poly(silamine), PEG-poly(silamine) block copolymer was prepared. The obtained block copolymer spontaneously associated with plasmid DNA (pDNA) to form polyplex micelles with a PAMA/pDNA polyion complex (PIC) core, and a PEG outer shell,
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as confirmed by ^1H NMR spectroscopy. Under physiological conditions, the PEG-poly(silamine)/pDNA polyplex micelles prepared at an N/P (number of amino groups in the copolymer/number of phosphate groups in pDNA) ratio above 3 were found to be able to condense pDNA, thus adopting a relatively small size (<150 nm) and an almost neutral surface charge (ζ〜+5 mV). The micelle underwent a pH-induced size variation (pH=7.4, 132.6 nm to. pH=4.0, 181.8 nm) presumably due to the conformational changes (globule-rod transition) of the poly(silamine) chain in response to pH, leading to swelling of the poly(silamine) inner shell at lowered pH. Furthermore, the micelles exhibited a specific cellular uptake into HuH-7 cells (hepatocytes) through asialoglycoprotein (ASGP) receptor-mediated endocytosis and achieved a far more efficient transfection ability of a reporter gene because of the installation of lactose at the end of PEG chain of the micelle. Therefore, the polyplex micelle composed of Ligand-PEG/poly(silamine) block copolymer would be a promising approach to a targetable and endosome disruptive nonviral gene vector. Less
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