2023 Fiscal Year Annual Research Report
ホウ素中性子捕捉療法のための多機能性ナノ薬剤の創製とEPR効果型腫瘍デリバリー
| Project/Area Number |
22KF0311
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| Allocation Type | Multi-year Fund |
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| Research Institution | Kumamoto University |
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Principal Investigator |
新留 琢郎 熊本大学, 大学院先端科学研究部(工), 教授 (20264210)
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| Co-Investigator(Kenkyū-buntansha) |
ISLAM WALIUL 熊本大学, 大学院先端科学研究部(工), 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 | multi-functional drug / BNCT / glycolysis inhibition / EPR-effect / ER/mitochondrial stress |
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| Outline of Annual Research Achievements |
We developed a water-soluble polymer drug namely styrene maleic acid (SMA) copolymer conjugated glucosamine and boric acid (SGB-complex). Initially this drug was designed for boron neutron capture therapy, but surprisingly we discovered that this complex can inhibit the cancer cell growth even without neutron irradiation. However, the precise chemical structure of SGB-complex and the detail mechanism of showing cytotoxicity was not clearly understood. During the fellowship period, we have investigated the exact chemical structure of the SGB-complex by means of UV-vis, infra-red, circular dichroism, NMR spectroscopy and liquid chromatography masa spectroscopy. Based on accumulating data, we conclude that the -NH2 group of glucosamine bound to -COOH group of SMA polymer by amide bond, and the boric acid (BA) bound to the glucosamine via cis-diol bond.
We also investigated possible mechanisms of cell killing effect by SGB-complex, and we confirmed that SGB-complex released free BA in tumor tissue pH and liberated BA compete with phosphate in phosphorylation of glucose to glucose 1-phosphate and inhibit the glycolysis of cancer cells. According to Warburg effect, in hypoxic state of cancer cells predominantly depend on energy production by glycolysis instead of TCA cycle. It means suppression of glycolysis of cancer cell will lead it to apoptosis. Moreover, the SGB-complex induced endoplasmic reticulum stress especially in hypoxia state which mimic the tumor tissue environment and turn to apoptosis. Taken together, SGB-complex inhibits the tumor growth with multiple mechanisms.
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[Journal Article] Styrene maleic acid polymer-encapsulated chlorophyll as a stable micellar nanoprobe for advanced anticancer photodynamic therapy2023
Author(s)
Waliul Islam, Hiroyasu Tsutsuki, Azizur Rahman, Ayaka Harada, Tianli Zhang, Katsuhiko Ono, Rayhanul Islam, Foysal Hossen, Takuro Niidome, Tomohiro Sawa, Jun Fang
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Journal Title
ACS Applied Biomaterials
Volume: 5
Pages: 10289-10302
DOI
Peer Reviewed
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