A Custom-Engineered Water-Soluble Peptide-Based Macrocyclic Polynuclear Gd³⁺-Chelated Paramagnetic Multimodal...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Nanotechnology

Background:

• Multimodal imaging probes integrate fluorescent biomarkers and magnetic resonance (MR) contrast agents for synergistic diagnostic information.
• Developing targeted probes is crucial for advancing biomedical diagnostics and understanding cellular processes.

Purpose of the Study:

• To synthesize and characterize a novel peptide-based multimodal contrast agent for cellular organelle-targeted imaging.
• To evaluate the agent's performance in fluorescence microscopy and MRI of live cells.

Main Methods:

• Custom-engineered peptide synthesis using Fmoc-solid phase peptide synthesis methodology.
• Integration of a hemicyanine (HCy) fluorescent dye with a macrocyclic polynuclear tri-Lys(DOTA-Gd3+) MRI contrast agent.
• Characterization of magnetic properties and relaxivity (r1).

Main Results:

• Successful synthesis of the HCy-Lys(DOTA-Gd3+)-Lys(DOTA-Gd3+)-Lys(DOTA-Gd3+)-Gly agent.
• Demonstrated high longitudinal relaxivity (r1 = 7.65 mM-1 s-1) and substantial magnetic moment.
• Effective application in live-cell mitochondrial-targeted confocal microscopy, 3D imaging, real-time monitoring, and multicolor imaging with T1-weighted MRI.

Conclusions:

• The developed peptide-based multimodal contrast agent offers enhanced MRI contrast and stable Gd3+ chelation.
• Its biocompatibility, water solubility, and multimodal imaging capabilities make it a promising tool for live-cell mitochondria-targeted diagnostics.
• This agent transcends limitations of single-modality imaging, paving the way for advanced biomedical diagnostics.