2004 Fiscal Year Final Research Report Summary
Design of the nanointerface for detection, recovery, and regeneration of abnormal proteins
| Project/Area Number |
14380412
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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 |
Biomedical engineering/Biological material science
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| Research Institution | Keio University |
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Principal Investigator |
FUJIMOTO Keiji Keio University, Faculty of Sci. & Tech., Associate Professor, 理工学部, 助教授 (70229045)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Poly-L-lysine / Poly(ethylene glycol) / β-sheet structure / Nanoparticle / Nanocarrier / Nanobiomaterial |
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| Research Abstract |
Polymeric nanoparicles have been paid to attention as a drug carrier. It is required that carriers are inert and non-toxic and are not accumulated or are degradable in the body. Therefore we selected poly-L-lysine (PLL) that is degradable polypeptide for a backbone of a nanoparticle. Because PLL exhibits structural changes among random, helix, and β-sheet by pH and temperature, we expect the stimuli-sensitive release of drugs from nanoparticles.
PLL was allowed to react with poly (ethylene glycol) (PEG) to improve the dispersion-stability and to prolong the lifetime in blood (mPEG-PLL polymer). Then, mPEG-PLL polymer was coupled with phosphatidic acid (PA) that acts as a hydrophobic site (mPEG-PLL-PA nanoparticle). The obtained polymers spontaneously aggregated into a nanoparticulate shape by the hydrophobic association among PA moieties. Whilst mPEG-PLL polymers were assembled to nanoparticles upon the formation of β-sheet structure in high pHs and high temperatures (mPEG-PLL nanoparticle). Both nanoparticles were 10-80nm in size and possessed the positive change. FITC-labeled nanoparticles were internalized into A431 cells. Adriamycin (ADR) that is an anticancer drug was incorporated into mPEG-PLL-PA nanoparticle more than mPEG-PLL nanoparticle because of PA's great hydrophobicity. However, drug release showed an opposite tendency. In pH4, release rate of ADR from mPEG-PLL nanoparticles was faster than that from mPEG-PLL-PA nanoparticles. Thereby survival rate of A431 cells decreased when they were treated with ADR-loaded mPEG-PLL nanoparticles.
We applied β-sheet association of the mPEG-PLL polymer to inhibition of protein aggregation. PLL tends to aggregate through β-sheet association by raising pH and temperature. This aggregation could be inhibited by adding the mPEG-PLL polymer. This suggests that the mPEG-PLL polymer is capable of inhibiting aggregation of abnormal proteins that cause conformational diseases.
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