Visualizing Lysosomal Positioning with a Fluorescent Probe Reveals a New Synergistic Anticancer Effect.

Abstract

The observation and discovery of lysosome dynamic alterations will greatly contribute to the in-depth understanding of lysosome biology and the development of new cancer therapeutics. To visualize lysosomal dynamics, here we have developed a lysosome-targetable fluorescent probe of NIM-3 showing integrated high selectivity, high photostability, and low cytotoxicity. With the aid of the excellent spatial and temporal imaging capability of NIM-3, three different types of motion of lysosomes were defined, and perinuclear accumulation of lysosomes in response to the pro-inflammatory cytokine stimulus was observed in various cells. More importantly, through lysosomal positioning studies, a new and potential anticancer therapy, i.e., the combination treatment of TNFα (tumor necrosis factor alpha) and chloroquine (CQ, a lysosomal pH elevator), was disclosed. The efficacy of the "CQ + TNFα" treatment was verified by different types of human cancer cells, and the anticancer mechanism may be partially attributed to lysosomal dilation.

• Authors: Kaixin Yu, Yufeng Ding, Hua Yu, Wencheng Zhu, Haitao Yu, Yanju Luo, Xujun Zheng, Yan Huang, Zhiyun Lu, Xiongjun Wang
• Journal: ACS sensors (ACS Sens) Vol. 7 Issue 7 Pg. 1867-1873 (07 22 2022) ISSN: 2379-3694 [Electronic] United States
• PMID: 35766996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorescent Dyes
• Tumor Necrosis Factor-alpha

Topics

• Diagnostic Imaging
• Fluorescent Dyes
• Humans
• Lysosomes
• Tumor Necrosis Factor-alpha