Related Experiment Video
Updated: Jan 6, 2026
Author Spotlight: Detection of Mitophagy in Caenorhabditis elegans and Mammalian Cells Using Organelle-Specific Dyes
Published on: May 19, 2023
A lysosome specific theranostic NO donor inhibits cancer cells by stimuli responsive molecular self-decomposition
Wuyang Hua1, Jian Zhao2, Xinyi Wang1
1Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China. 101010898@seu.edu.cn.
Abstract:
The anticancer mechanism of NO is difficult to study owing to its short lifetime and high reactivity. Thus, a theranostic anticancer NO donor assembled with NO on-demand release abilities, accurate lysosome location capabilities and signal feedback behavior was developed. Profiting from the theranostic properties, the specific mechanism was comprehensively studied. Spectral and cell imaging studies revealed that the as prepared NO donors could release NO in solution or within cancer cells. Fluorescence co-dyeing experiments demonstrated that Mo-Nap-NO entered lysosomes specifically and disrupted them after being triggered by light. Upon irradiation with 460 nm visible light, both the donors demonstrated considerable in vitro anticancer effects. A further mechanistic study showed that after entering the lysosome and being triggered by 460 nm irradiation, NO ruptured the lysosome, resulting in the release of cathepsin D into the cytosol, which activated the caspase3 mediated apoptosis pathway.
Insights
Researchers developed a novel theranostic nitric oxide (NO) donor for cancer therapy. This innovative NO donor precisely targets cancer cells, releases NO on-demand, and triggers apoptosis by disrupting lysosomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Studying the anticancer mechanism of nitric oxide (NO) is challenging due to its short half-life and high reactivity.
- Developing targeted therapies with controlled NO release is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a theranostic anticancer NO donor with on-demand release, lysosome-targeting, and signal feedback capabilities.
- To comprehensively investigate the anticancer mechanism of the developed NO donor.
Main Methods:
- Synthesis of a novel theranostic NO donor (Mo-Nap-NO).
- Spectral and cell imaging studies for NO release verification.
- Fluorescence co-dyeing for lysosome localization and disruption assessment.
- In vitro anticancer assays upon visible light irradiation.
Main Results:
- The NO donor successfully released NO in solution and within cancer cells.
- Mo-Nap-NO specifically localized to lysosomes and disrupted them upon 460 nm light irradiation.
- Significant in vitro anticancer effects were observed, mediated by lysosomal disruption and subsequent apoptosis induction.
Conclusions:
- The developed theranostic NO donor enables precise control over NO release and lysosome targeting for cancer therapy.
- The study elucidated a novel anticancer mechanism involving light-triggered lysosomal rupture and caspase-3 mediated apoptosis.
- This approach offers a promising strategy for developing effective and mechanism-specific cancer treatments.
