1999 Fiscal Year Final Research Report Summary
Design of Polymeric Supramolecular-assembly for Targeted Therapy of Liver
| Project/Area Number |
09308035
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Tokyo Institute of Technology |
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Principal Investigator |
AKAIKE Toshihiro Dept. of Biomolecular Engineering, Tokyo Institute of Technology, Prof., 生命理工学部, 教授 (30101207)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEI Yoshiyuki Juntendo Univ. School of Medicine, Assis. Prof., 医学部, 講師 (10306954)
MARUYAMA Atsushi Dept. of Biomolecular Engineering, Tokyo Institute of Technology, Assis. Prof., 生命理工学部, 助手 (40190566)
WATANABE Yoshifumi Dept. of Biomolecular Engineering, Tokyo Institute of Technology, Prof., 生命理工学部, 助手 (40231013)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Liver specific Therapy / Hepatocyte / Asialoglycoprotein-receptor / Biomimetics / Gene-transfection of hepatic lectin / Hyaluronic acid receptor / nanoparticle / polymeric supra-molecular assembly |
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| Research Abstract |
In order to design amphiphilic glycopolymers for targeted therapy of liver, oligosaccharide-carrying polymers which can recognize various kinds of liver cells were synthesized. Polymeric micel of lactose-carrying polystyrene (PVLA) and its coated nanoparticle were found out to be efficiently incorporated into hepatocyte mediated by asialogly coprotein receptor (ASGP-R). Poly (lactic acid) nanopaticles coated with PVLA involving caspase inhibitor (Z-Asp) were successfully targeted to hepatocytes in liver and effectively released to rescue hepatitis related cell apoptosis.
The transfections of ASGP-R consisting of hepatic lectin 1 and 2 (HL-1,2) into CHO-Kl cells indicated that oligomeric association of HL-1 and 2 are responsible to higher cell-recognition of PVLA-coated nanoparticle.
Based on the finding, dendritic graft copolymers of poly (L-lysine) main chain and arabiogalactan (β-galactos rich multi-anntenary polysaccharide) as DNA carrier were synthesized and evaluated for the recognition by ASGP-R of hepatocytes and hepatoma cells.
Hyaluronic acid carrying poly (L-lysine) were also synthesized to be applied for specific DNA-targeting to liver sinusoidal endothelial cells.
The concept of supramolecular-assembly systems such as polymeric micels, nanoparticles and polymer complex are successfully proposed.
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