2022 Fiscal Year Research-status Report
Externally Triggered Nanomachine for Breast Cancer Theranostics
| Project/Area Number |
20K05260
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| Research Institution | Gunma National College of Technology |
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Principal Investigator |
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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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | theranostics nanozyme / normoxia condition / B16-F10 melanoma / ATPase activity / breast cancer / noninvasive chemotherapy |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
The reasons are: (i) opportunity to invite a foreign researcher for collaboration, or (ii) participation in an international conference. During 2022 there was not possibility to travel oversea or inviting of foreign collaborator due to the strict restrictions related to the pandemic of COVID-19.
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