4.8 Article

Library Screening to Identify Highly-Effective Autophagy Inhibitors for Improving Photothermal Cancer Therapy

Journal

NANO LETTERS
Volume 21, Issue 22, Pages 9476-9484

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c02825

Keywords

photothermal therapy; autophagy inhibition; library screen; nanodrugs; cancer

Funding

  1. National Natural Science Foundation of China [31871010, 32071383]

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The study revealed that small molecular inhibitors can enhance the efficiency of photothermal cancer therapy, with daurisoline being the most effective inhibitor that disrupts autophagosome formation and fusion process. Combination treatment with nanodrugs loaded with daurisoline and indocyanine green was more efficient than individual modalities, leading to complete inhibition of tumor growth.
The small molecular inhibitor-associated down-regulation 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.

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