2020 Fiscal Year Research-status Report
Development of novel tumor-targeting nanoparticles for malignant brain tumor neutron capture therapy and diagnosis
| Project/Area Number |
20K07672
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
ザボロノク アレクサンドル 筑波大学, 医学医療系, 助教 (20723117)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
中井 啓 筑波大学, 医学医療系, 准教授 (50436284)
鶴淵 隆夫 筑波大学, 医学医療系, 講師 (70778901)
MATHIS BRYAN 筑波大学, 医学医療系, 助教 (80794635)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | BNCT / glioma / nanoparticles / tumor targeting |
|---|
| Outline of Annual Research Achievements |
In the 2020 fiscal year, we have performed the mechanochemical synthesis of the boron core of nanoparticles using ultrasonic cavitation. Additional physical, chemical and electron-microscopic analyses of the synthesized nanoparticles have been accomplished. The stabilization of the particles has been performed using a well-established polymer compound, hydroxyethylcellulose, which played the role of the substrate and provided the stability of the particles in the solution over time. The core boron nanoparticles have been found stable in water solutions and non-toxic for human glioma cells without neutron irradiation. As a part of the complex system, gold nanoparticles have been created using established methods with reduction of a gold hydrochlorate solution by citrate, and efforts to establish the complex system have been made using a polymer substrate. ApoB-29 lipoprotein synthesis has been initiated, and functionalization routes have been studied. The cell line panel has been adopted, and human glioma cell lines have been analyzed for further cell and animal experiments. Additionally, compound delivery options have been studied and liposomal carriers have been evaluated as a part of the complex delivery system.
|
| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
The research progress has been slightly delayed due to delays in the delivery of certain compounds to the laboratory and limited access to the research facilities during the quarantine period. We have faced certain difficulties in the elemental analysis of boron due to the inability to process hydroxyethylcellulose as a substrate for the complex compound. The alternative polymer substrate, hyaluronic acid, has been proposed to solve this issue.
|
| Strategy for Future Research Activity |
Future plans include assembly of the boron-gold complex using the alternative substrate, studying the routes of and performing its functionalization with tumor-targeting molecules of ApoB-29, further in vitro evaluation of the compound accumulation and cytotoxicity, studying tumor cell-killing effect of the synthesized nanocomplexes, and the ways of dosimetry based on gold component activation after irradiation with thermal and epithermal neutrons. Selection of most appropriate glioma cell lines for further animal experiments and initiation of the animal experiments, including nanoparticle toxicity evaluation, is also planned, including the design of the scanning spectrometry to calculate the boron dose. Further research will include animal experiments with tumor models and their treatment using the synthesized nanoparticles and neutron irradiation.
|
| Causes of Carryover |
In 2020 planned travel expenses were not used due to the inability to travel due to the quarantine and the fact that most conferences were cancelled. Therefore we decided to move that unused amount to the next fiscal year.
|
