Journal de la science cellulaire et de la thérapie
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Abstrait

Fibrin-Targeting, Peptide Amphiphile Micelles as Contrast Agents for Molecular MRI

Eun Ji Chung, Federico Pineda, Kathryn Nord, Gregory Karczmar, Seon-Kyu Lee and Matthew Tirrell

Magnetic resonance imaging (MRI) provides a nonionizing and safe imaging modality for cancer diagnostics. Here, we took advantage of the fibrin deposition that is characteristic of tumors and the ability to incorporate multiple functionalities within peptide amphiphile micelles (PAMs) to design a new class of contrast agents for molecular MRI. We report on synthesis, formulation, and preliminary tests for MRI of spherical PAMs that were self-assembled by combining 18:0 PE-DTPA (Gd) and peptide amphiphiles containing the fibrin-binding pentapeptide, cysteinearginine- glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to micelles increased the average particle size and zeta potential, and T1 relaxivities of CREKA-Gd PAMs (per mmol of Gd) were found to be comparable to contrast agents which are used routinely in clinical settings at 1.5T and 3T. Moreover, when murine fibroblasts were cultured with CREKA-Gd PAMs, no cytotoxicity was demonstrated and cell viability was comparable to that of PBS-treated controls for up to 3 days.Our study provides proof-of-concept of CREKA-Gd PAMs as contrast agents for molecular MRI, and a facile strategy for incorporating contrast agents and bioactive molecules into nano carriers to develop safe, targeted diagnostic carriers for clinical application.