2021 Fiscal Year Research-status Report
Therapeutic polymer nanoreactor with site-specific activation of targeting Warburg metabolism for metastatic breast cancer treatment
| Project/Area Number |
20K20209
|
|---|
| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
|---|
Principal Investigator |
LI JUNJIE 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (80869892)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | immunotherapy / nanoreactors / pyroptosis / self-assembly / vesicles / tumor metabolism |
|---|
| Outline of Annual 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.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
1. We confirmed that the glucose and lactate could be simultaneously consumed by oxidase-loaded vesicular nanoreactor with accompanying ROS production, which aggravated nutrients metabolic stress to induce cancer cell death.
2. As a accident discovery, nanoreactors could induce an immunostimulatory form of cell death by pyroptosis, which has the great potential to prime anti-tumor immune responses.
|
| Strategy for Future Research Activity |
1. In vivo anti-tumor therapy is ongoing.
2. Combination therapy (nanoreactor plus anti-PD-1 immunotherapy) is also ongoing.
|
| Causes of Carryover |
Some reagents arrived later.
|
