Dehydroberberine Analogue Nanoassemblies for Inducing and Self-Reporting Mitochondrial Dysfunction in Tumor Cells

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Theranostics

Background:

• Mitochondria-targeting probes are promising for cancer theranostics, but lack tumor cell selectivity.
• Existing probes struggle to differentiate between tumor and normal cells, limiting treatment efficacy.
• Need for improved selectivity and cytotoxicity in mitochondria-targeting cancer agents.

Purpose of the Study:

• To develop selective mitochondria-targeting fluorescent probes for cancer theranostics.
• To enhance the delivery and cytotoxicity of probes in tumor cells.
• To create a self-reporting system for mitochondrial dysfunction in cancer cells.

Main Methods:

• Synthesized ten fluorescent dehydroberberine derivatives (B1-B10).
• Introduced tetraphenylborate (TPB-) to create self-assembled organic nanoassemblies (B3NPs).
• Utilized electrostatic interaction-driven anion-exchange for enhanced cellular delivery.
• Performed fluorescence imaging to track probe localization and mitochondrial dysfunction.
• Assessed cytotoxicity against multiple human tumor and normal cell lines.

Main Results:

• B3NPs demonstrated enhanced delivery into HeLa cells via anion-exchange.
• Probes initially localized in mitochondria, induced dysfunction, and migrated to the nucleus.
• Real-time monitoring of mitochondrial dysfunction through fluorescence translocation was achieved.
• B3NPs exhibited significantly higher cytotoxicity against seven tumor cell lines versus normal cells.

Conclusions:

• Self-assembly into nanoassemblies improves the selectivity and cytotoxicity of mitochondria-targeting agents.
• The developed B3NPs show potential as theranostic agents for enhanced cancer treatment.
• This approach offers a strategy to overcome selectivity limitations in cancer theranostics.