Abstract
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.
Highlights
Magnetic resonance imaging (MRI) is a preferred diagnostic imaging modality of cancer evaluation because it is noninvasive, does not use ionizing radiation, and provides strong soft tissue contrast [1]
In order to integrate the molecular targeting capabilities of peptide amphiphile micelles (PAMs) and the diagnostic performance of MRI, we combined peptide amphiphiles (PA) consisting of the CREKA peptide and 18:0 PEDTPA (Gd) to self-assemble micelles that can be utilized as molecular MRI contrast agents for tumor-targeting
Stock solutions of 100 μM CREKA-Gd or control-Gd PAMs were used to confirm the presence of small spheroidal micelles and Dynamic Light Scattering (DLS) measurements were determined at 90° and 637 nm using a Brookhaven Instruments (Holtzville, NY, USA) system consisting of a BI-200SM goniometer and a BI-9000AT autocorrelator (N=3)
Summary
Magnetic resonance imaging (MRI) is a preferred diagnostic imaging modality of cancer evaluation because it is noninvasive, does not use ionizing radiation, and provides strong soft tissue contrast [1]. Our group has successfully developed a fluorescently-labeled, fibrin-binding peptide amphiphile micelle (PAM) for cancer targeting using the pentapeptide, cysteine-arginine-glutamic acid-lysinealanine (CREKA) [4,6,7]. In order to integrate the molecular targeting capabilities of PAMs and the diagnostic performance of MRI, we combined peptide amphiphiles (PA) consisting of the CREKA peptide and 18:0 PEDTPA (Gd) to self-assemble micelles that can be utilized as molecular MRI contrast agents for tumor-targeting.
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