2020 Fiscal Year Research-status Report
Design and application of short chain fatty acid nanoparticles for cancer and obesity therapeutics
| Project/Area Number |
20K20194
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SHASHNI BABITA 筑波大学, 数理物質系, 特任助教 (90869629)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | Short-chain fatty acid / cancer / radio-sensitizer / radiation therapy / NASH / SCFA nanoparticle / controlled release |
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| Outline of Annual Research Achievements |
1.We successfully synthesized PEG-b-PVRs (R=Propionic, Butyric acid) via RAFT polymerization with a yield of 86.6% for PEG-b-PV(Pr) and 87.3% for PEG-b-PV(Bu). We also successfully prepared the nano-sized propionic acid nanoparticle (PNP) and butyric acid nanoparticle (BNP), which were were stable under various pH (1-12).
2.B16F10 metastasis melanoma model: We prepared metastasis model by injection B16F10 melanoma intravenously and started the administration of BNP and PNP by free drinking one day prior to cancer inoculation to the experimental end point day 11 (30 mM). We confirmed that BNP and PNP-treated group both decreased the metastatic nodules in the lungs and did not exert any damage to organs in contrast to LMW SCFAs (30 uM).
3. Radio-sensitizing evaluation: We confirmed that intraperitoneally injection of BNP (500 mg/kg) 24 h before the irradiation, greatly sensitizes the cancer cells to the radiotherapy which was confirmed by decreased tumor volume and weight as compared to irradiated tumor control, in contrast to butyric acid-treated group.
4. Nonalcoholic steatohepatitis (NASH): Free drinking of SCFA nanoparticles (100 mM) by mice fed with choline-deficient, L-amino acid defined high fat diet for 8 weeks, confirmed that BNP prevented NASH and liver fibrosis.
5. Diabetes: In a diabetic mice, we administered our sample and LMW SCFA (60 mM) as free drinking for 37 days and confirmed that BNP and the conventional exenatide improved glucose utilization and pancreas health without exerting toxicity as compared to LMW SCFA.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Because we started several models simultaneously, so we could accomplish much more than we expected. We will continue to make effort next year as well to conduct experiments, publishing our work and showcasing our work to the scientific community.
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| Strategy for Future Research Activity |
Our next year’s plan is to find suitable model for obesity and confirm the efficacy of our SCFA nanoparticles. In addition, we will make effort to finish the pharmacokinetics of our nanoparticles in various disease models NASH, cancer, and radiation therapy via different routes.
We would also like to focus our time to investigate the mechanism of efficacy on various disease models. In addition, once we achieve suitable data, we would like to publish our work and present in several domestic and international conferences.
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