Mitochondria-Targeted Two-Photon Fluorescent Photosensitizers for Cancer Cell Apoptosis via Spatial Selectability

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Organelle-targeted photosensitizers induce cell apoptosis.
• Mitochondria are key targets for cancer therapy due to their role in metabolism and apoptosis.
• Two-photon (TP) fluorescence microscopy offers deep-tissue imaging with reduced photodamage.

Purpose of the Study:

• Design, synthesize, and investigate novel mitochondrial-targeted TP fluorescent photosensitizers (TP-tracers).
• Evaluate their performance in complex biological environments and for in vivo imaging.
• Assess their potential for TP-activated cancer cell apoptosis and phototherapy.

Main Methods:

• Synthesis of novel TP-tracers.
• Characterization of TP properties, anti-interference capabilities (cations, anions, amino acids, pH), and cytotoxicity.
• In vitro and in vivo imaging in living cells, Drosophila brains, and zebrafish.
• Evaluation of mitochondria-targeting efficiency and induction of cell apoptosis.
• Pharmacokinetic studies.

Main Results:

• TP-tracers demonstrated excellent anti-interference capabilities and stability in complex biological settings.
• Successful fluorescence imaging in living cells, Drosophila brains, and zebrafish with low cytotoxicity.
• Efficient mitochondria-targeting and TP-activated cancer cell apoptosis with high single-cell selectivity.
• Pharmacokinetic studies showed no accumulation of MitoY2 in rats.

Conclusions:

• The developed TP-tracers possess desirable properties for mitochondria-targeting and TP fluorescence imaging.
• These molecules enable precise, selective cancer cell apoptosis induction via TP activation.
• The findings highlight the significant potential of these TP-tracers in advanced phototherapy applications.