2023 Fiscal Year Annual Research Report
分子技術を駆使したSN-38二量体設計と新規抗がん用ナノ薬剤の創出
| Project/Area Number |
22KF0036
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| Allocation Type | Multi-year Fund |
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| Research Institution | Tohoku University |
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Principal Investigator |
笠井 均 東北大学, 多元物質科学研究所, 教授 (30312680)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAR SANJAY 東北大学, 多元物質科学研究所, 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Keywords | SN-38 / Homodimer / Disulfide linker / Prodrug / Fabrication / Nanoparticles |
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| Outline of Annual Research Achievements |
SN-38 homodimers (9 compounds) and SN-38-indoximod conjugates (with and without disulphide bond) were synthesized in highly efficient yield, followed by fabricated as nano-prodrugs by reprecipitation method. The fabricated nano-prodrug of SN-38 homodimers and SN-38-indoximod conjugate having disulphide bond with 0% and 10% PS80, respectively, were not aggregated in one week stored at 4 °C due disulphide bond may favour the nanoparticle preparation and dispersion stability. Whereas nano-prodrugs of SN-38-indoximod conjugate without disulphide bond with 0/1/10/100% PS80 were aggregated after fabrication. 80-160 nm sized nanoparticles were observed in fabricated nano-prodrugs of SN-38 homodimers and SN-38-indoximod conjugate having disulphide bond (with 10% PS80) in SEM image.
One SN-38 homodimer showed promising in vitro anticancer activity against cancer cells. This result was supported by drug release study under GSH condition in which >85% of SN38 was released from prodrug in 6 h in the presence of GHS. Whereas prodrug SN-38-indoximod conjugate without disulphide didn’t release SN38 under GSH environment due to absence of disulphide bond containing linker. Therefore, it didn’t show in vitro anti-cancer activity against either A549 cells or MCF7 cells.
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