| Project/Area Number |
19K08112
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52040:Radiological sciences-related
|
|---|
| Research Institution | National Institute of Advanced Industrial Science and Technology |
|---|
Principal Investigator |
Misawa Masaki 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (60358083)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
新田 尚隆 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (60392643)
松本 孔貴 筑波大学, 医学医療系, 助教 (70510395)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 金ナノ粒子 / X線 / 放射線治療 / 活性酸素 / 超音波 / パイロトーシス / 炎症性サイトカイン / 細胞性障害分子パターン / 細胞障害性分子パターン / 増感剤 |
|---|
| Outline of Research at the Start |
局所投与により高濃度の増感剤を腫瘍周囲に分布させ、超音波照射を利用して金ナノ粒子増感剤の血管および間質透過性を高めることで腫瘍集積を大幅に高めるauroporationによる投与方法の有効性を動物モデルで検証するとともに、超音波照射に応答する標的指向型金ナノ粒子放射線増感剤を開発する。
|
| Outline of Final Research Achievements |
Enhancement of radiosensitization was aimed in this animal study by using gold nanoparticles as a radiosensitizer, which could develop a new branch of radiotherapy. Locally administrated gold nanoparticles were externally stimulated by focused ultrasound waves and their optimized protocol and conditions were searched for enhanced permeability through tumors by intruding blood vessels and interstitial tissues. We also found that damage-associated molecular patterns were released from the tumor exposed to therapeutic X-ray, which would lead to pyrotosis, also know as inflammatory programmed cell death pathway. After B16 melanoma cells were irradiated with large dose of X-ray, these molecular patterns were collected and adsorbed on the surface of gold nanoparticles. Together with appropriate adjuvant, the molecular pattern-capped gold nanoparticles showed an enhanced radiosensitization not only at the irradiated tumor, but also at the non-irradiated tumor to a degree.
|
| Academic Significance and Societal Importance of the Research Achievements |
高齢化が進行するなか、体への負担が少ないがん治療法として、今後、放射線治療が選択される機会が増えるであろう。放射線治療では、正常組織の被ばくを低減し、腫瘍に線量を集中することが重要だが、照射方法の改良のみでは、浸潤性やびまん性の複雑な形状のがん組織に線量集中できない。金ナノ粒子増感剤を、がん細胞選択的に取り込ませた後、放射線照射する増感剤併用治療により、細胞レベルで線量制御が可能となり、正常組織を温存し、取り残しによる再発を防ぐ効果的な放射線治療が実現する。
|
