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Library Screening to Identify Highly-Effective Autophagy Inhibitors for Improving Photothermal Cancer Therapy
Li Wang1, Yitong Wang2, Wei Zhao3
1Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, P. R. China.
Abstract:
The small molecular inhibitor-associated downregulation of autophagy can remarkably enhance the efficiency of photothermal cancer therapy. To identify a more effective autophagy inhibitor, we screened a library of 20 compounds and found chloroquine, hydroxychloroquine, dauricine, and daurisoline were more efficient than the others to improve the photothermal killing of cancer cells. Interestingly, the four agents all disturb the autophagosome formation and fusion process, indicating it is a promising target to enhance cancer therapeutic efficiency. Among the four agents, daurisoline was identified to be the most efficient one. It reduced the viability of cancer cells treated by low-energy photothermal therapy from 86.27% to 32.92%. Finally, the combination treatment mediated by nanodrugs loaded with daurisoline and indocyanine green was more efficient than the individual modalities, resulting in complete inhibition of tumor growth. The study gives new inspiration to autophagy modulation-associated photothermal therapy and other therapeutic modalities for cancer treatment.
Insights
Daurisoline enhances photothermal cancer therapy by inhibiting autophagy, significantly reducing cancer cell viability. Combination therapy with nanodrugs and indocyanine green achieved complete tumor growth inhibition.
Area of Science:
- Oncology
- Cell Biology
- Biomedical Engineering
Background:
- Autophagy inhibition enhances photothermal cancer therapy.
- Identifying effective autophagy inhibitors is crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To screen compounds for enhanced autophagy inhibition in photothermal therapy.
- To evaluate daurisoline as a potent autophagy inhibitor for cancer treatment.
Main Methods:
- Screened a library of 20 compounds for autophagy inhibition.
- Assessed the efficacy of chloroquine, hydroxychloroquine, dauricine, and daurisoline.
- Investigated the effect of daurisoline on cancer cell viability and tumor growth.
- Utilized nanodrugs loaded with daurisoline and indocyanine green for combination therapy.
Main Results:
- Chloroquine, hydroxychloroquine, dauricine, and daurisoline were identified as effective autophagy inhibitors.
- Daurisolne significantly reduced cancer cell viability from 86.27% to 32.92% under photothermal therapy.
- Combination therapy with daurisoline-loaded nanodrugs and indocyanine green resulted in complete tumor growth inhibition.
Conclusions:
- Autophagosome formation and fusion are promising targets for enhancing cancer therapy.
- Daurisolne is a highly efficient autophagy inhibitor for photothermal cancer therapy.
- Combination therapy offers a superior strategy for cancer treatment, inspiring new therapeutic approaches.
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