Luminescent Peptide/Lanthanide(III) Complex Conjugates with Push-Pull Antennas: Application to One- and Two-Photon...

Area of Science:

• Inorganic Chemistry
• Bioimaging
• Cell Biology

Background:

• Lanthanide(III) complexes offer valuable luminescence for microscopy.
• Challenges exist in delivering these complexes into cells for imaging, especially using two-photon (2P) microscopy.
• Developing effective cell-penetrating peptide (CPP) conjugates is crucial for in vivo applications.

Purpose of the Study:

• To synthesize and characterize novel lanthanide(III) complexes with enhanced 2P absorption properties.
• To create and evaluate peptide-lanthanide(III) complex conjugates for live cell imaging.
• To demonstrate the feasibility of 2P confocal microscopy for intracellular luminescence analysis.

Main Methods:

• Synthesis and spectroscopic characterization of lanthanide(III) complexes with picolinate-based ligands (L1, L2).
• Conjugation of selected complexes (Tb(L1), Eu(L2)) to cell-penetrating peptides (ZF5.3, TP2).
• Evaluation using one-photon (1P) time-gated and 2P confocal microscopy for cellular uptake and luminescence imaging.

Main Results:

• Novel Ln³⁺ complexes with extended picolinate antennas were synthesized, showing good 2P absorption.
• Conjugation to peptides did not alter the luminescence properties of the complexes.
• ZF5.3 peptide conjugates successfully entered cells, enabling both 1P and 2P imaging.
• 2P confocal microscopy allowed detailed characterization of intracellular luminescence properties.

Conclusions:

• Peptide conjugation is a viable strategy for delivering Ln³⁺ complexes into live cells.
• The developed ZF5.3[Tb(L1)] conjugate is effective for 1P and 2P live cell imaging.
• This approach opens new possibilities for functional luminescent probes in advanced cellular imaging.