Enhanced cell death imaging using multivalent zinc(II)-bis(dipicolylamine) fluorescent probes

Area of Science:

• Biomedical Imaging
• Molecular Probes
• Cell Biology

Background:

• Accurate detection of cell death is crucial for diagnosing and monitoring various pathologies.
• Zinc(II)-bis(dipicolylamine) (Zn2BDPA) coordination complexes target phosphatidylserine on dead/dying cells.
• Fluorescent Zn2BDPA probes are established cell death imaging agents.

Purpose of the Study:

• To compare the membrane targeting efficacy of bis-Zn2BDPA-SR and tetra-Zn2BDPA-SR probes.
• To evaluate the impact of multiple Zn2BDPA units on probe performance.
• To assess the in vivo applicability of these probes in animal models of cell death.

Main Methods:

• Synthesis and characterization of bis-Zn2BDPA-SR and tetra-Zn2BDPA-SR probes.
• Vesicle and cell microscopy studies to assess probe-membrane interactions.
• In vivo imaging studies in rat and mouse models of necrosis, atrophy, and traumatic brain injury.

Main Results:

• Higher numbers of Zn2BDPA units improved probe selectivity for phosphatidylserine-rich vesicles.
• Increased probe localization at the plasma membrane of dead and dying cells was observed with more targeting units.
• Tetra-Zn2BDPA-SR showed greater accumulation at cell death sites across all tested animal models compared to bis-Zn2BDPA-SR.

Conclusions:

• Multivalent Zn2BDPA probes demonstrate enhanced selectivity and localization for imaging cell death.
• Tetra-Zn2BDPA-SR is a promising candidate for effective cell death imaging in both in vitro and in vivo settings.
• These findings support the development of advanced molecular probes for pathological condition monitoring.