| Project/Area Number |
20K20209
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Kyushu University (2022)
Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine (2020-2021) |
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Principal Investigator |
LI JUNJIE 九州大学, 先導物質化学研究所, 准教授 (80869892)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Immunotherapy / Nanoreactors / Pyroptosis / Self-assembly / Vesicles / Tumor metabolism / immunotherapy / nanoreactors / pyroptosis / self-assembly / vesicles / tumor metabolism / vesicle / nanoreactor / drug delivery |
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| Outline of Research at the Start |
The applicant will exploit the nanoreactor in the tumor-specific activation to simultaneously suppress breast tumor growth and metastasis. The glucose and lactate will be simultaneously consumed by oxidase-loaded nanoreactor with accompanying ROS production, which will aggravate metabolic stress.
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| Outline of Final Research Achievements |
We developed a oxidase-loaded nanoreactor that could specifically render tumor cells immunogenic by pyroptosis, a highly pro-inflammatory programmed cell death. Of particular interest, the vesicular system based on PICsomes is highly modular, generic, and simple and could be adapted to customize various kinds of activatable nanoreactors based on triggerable cross-linking membrane networks. As a consequence, the nanoreactor with self-boosting catalytic glucose oxidation could protect oxidase to initiate pyroptosis in the long term. We confirmed that not only glucose oxidase-loaded but also lactate oxidase-loaded nanoreactors could induce pyroptosis. In combination with immunotherapy, the antitumor efficacy has been confirmed.
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| Academic Significance and Societal Importance of the Research Achievements |
1. Scientific significance: a generic method has been developed to construct smart oxidase-loaded nanoreactor for specifically targeting tumor metabolism.
2. Social significance: Our nanoreactors can increase the potential of immunotherapy to bring more benefits to cancer patients.
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