研究課題/領域番号 |
20K05260
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研究種目 |
基盤研究(C)
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配分区分 | 基金 |
応募区分 | 一般 |
審査区分 |
小区分28030:ナノ材料科学関連
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研究機関 | 群馬工業高等専門学校 (2021-2022) 埼玉大学 (2020) |
研究代表者 |
ルカノフ アレクサンダー 群馬工業高等専門学校, 物質工学科, 准教授 (40751566)
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研究期間 (年度) |
2020-04-01 – 2024-03-31
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研究課題ステータス |
交付 (2022年度)
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配分額 *注記 |
4,290千円 (直接経費: 3,300千円、間接経費: 990千円)
2022年度: 390千円 (直接経費: 300千円、間接経費: 90千円)
2021年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
2020年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
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キーワード | theranostics nanozyme / normoxia condition / B16-F10 melanoma / ATPase activity / breast cancer / noninvasive chemotherapy / Theranostic nanomachine / artificial nanozyme / carbon nanodots / breast cancer cells / Nanozyme / Carbon nanodots / Photosensitization / Nanoparticles / Nanomachines / Cancer cells / Light therapy / Theranosctics |
研究開始時の研究の概要 |
A new design of light-triggered nanomachines, which harvest and convert irradiation energy into reactive oxygen species is proposed. They are made from nontoxic carbon nanodots and aptamer. The nanomachines can target cancer cells with its aptamer and induce their programmed death by singlet oxygen.
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研究実績の概要 |
A photo-oxidative nanozyme for cancer theranostics was demonstrated at normoxic conditions on breast cancer B16-F10 mouse melanoma with high metastatic potential. The experimental data revealed that the metastatic migration might be controlled by nanozyme and applied near-infrared energy dosage. The biocompatibility of the nanozyme was proved on ATPase activity of intact mitochondria and sub-mitochondrial particles, on diamine oxidase activity of liver and kidney fractions in dark mode, as well as on non-illuminated adenocarcinoma human alveolar basal epithelial cells (A549) and human liver cancer cells (HepG2). The effective therapeutic amount (~50 mg/l) was found to be 10-fold lower than the threshold dose (> 500 mg/l) and it did not influenced the signal pathways of the healthy cells.
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現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Currently the opportunity to develop the nanozyme as a platform for nanocarrier or an integral part of drug delivery nano-system is investigated. The nanocarrier is a subject of decoration with ligands (as antibodies or aptamers) for enhanced identification and improved binding to the overexpressed or abnormal membrane receptors on the cancer cells, as well as improved proceeding of induced receptor-mediated endocytosis. The possibility to inhibit the exosome signaling during maintaining breast cancer cells within the tumor is also under investigation. Novel microscopic approach to observe the cancer cells communication is applied. The experimental progressing is evaluated to perform as rather smoothly and the circumstances at the moment do not create a reason for any concerns.
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今後の研究の推進方策 |
The future work is focused on the design and engineering of biocompatible and stimuli-sensitive nanozyme that is programmed to realize prolonged circulation in the body, to overcome the complex biological barriers of proliferative tumors and to be accumulate inside its interstitium. The planned experiments are aiming to develop the nanozyme also as a platform for construction of nanomachine that might responds to the specificity and changes in the tumor microenvironment, as well as the opportunity to be applied into chimeric antigen receptor therapy (CAR-T). In that case the nanomachine will be designed to operate in synergistic way with other bioagents and drugs in order to create a therapeutic window for effective T-cell treatment of solid malignancies.
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