Biocompatible Peptide-Coated Ultrasmall Superparamagnetic Iron Oxide Nanoparticles for In Vivo Contrast-Enhanced Magnetic Resonance Imaging

Abstract

The biocompatibility and performance of reagents for in vivo contrast-enhanced magnetic resonance imaging (MRI) are essential for their translation to the clinic. The quality of the surface coating of nanoparticle-based MRI contrast agents, such as ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), is critical to ensure high colloidal stability in biological environments, improved magnetic performance, and dispersion in circulatory fluids and tissues. Herein, we report the design of a library of 21 peptides and ligands and identify highly stable self-assembled monolayers on the USPIONs' surface. A total of 86 different peptide-coated USPIONs are prepared and selected using several stringent criteria, such as stability against electrolyte-induced aggregation in physiological conditions, prevention of nonspecific binding to cells, and absence of cellular toxicity and contrast-enhanced in vivo MRI. The bisphosphorylated peptide 2PG-S*VVVT-PEG4-ol provides the highest biocompatibility and performance for USPIONs, with no detectable toxicity or adhesion to live cells. The 2PG-S*VVVT-PEG4-ol-coated USPIONs show enhanced magnetic resonance properties, r (2.4 mM·s) and r (217.8 mM·s) relaxivities, and greater r/ r relaxivity ratios (>90) when compared to those of commercially available MRI contrast agents. Furthermore, we demonstrate the utility of 2PG-S*VVVT-PEG4-ol-coated USPIONs as a T contrast agent for in vivo MRI applications. High contrast enhancement of the liver is achieved as well as detection of liver tumors, with significant improvement of the contrast-to-noise ratio of tumor-to-liver contrast. It is envisaged that the reported peptide-coated USPIONs have the potential to allow for the specific targeting of tumors and hence early detection of cancer by MRI.

Use of magnetic fields and nanoparticles to trigger drug release and improve tumor targeting

“…To reduce toxicity, SPIONs are often coated with biocompatible polymers such as dextran, PEG, and PEI (Muthiah, Park, & Cho, 2013). There have also been attempts to encapsulate nanoparticles in lipids (H.-C. Huang et al, 2009;Liang, Zhang, Miao, Li, & Gan, 2017) and peptides (Chee et al, 2018) to reduce toxicity and improve circulation time. Others have also found that cytotoxicity is both coating-and size-dependent (Feng et al, 2018).…”

A Review on Iron Oxide‐Based Nanoarchitectures for Biomedical, Energy Storage, and Environmental Applications

“…Apart from polymeric coating (e.g., PEG, PEI, PAA), effective MRI contrast agents based on iron oxide NPs with different surface coatings have been reported in the literature. Previously, peptide coating has been shown to enhance the r 1 (2.4 m m −1 s −1 ) and r 2 relaxivities (217.8 m m −1 s −1 ) of ultrasmall SPIONs (USPIONs) with higher relaxivity ratios (>90) relative to commercially available MRI contrast agents . Furthermore, peptide‐coated USPIONs could show high contrast enhancement of the liver for detection of liver tumors.…”

Peptide-functionalized NaGdF4 nanoparticles for tumor-targeted magnetic resonance imaging and effective therapy

“…Peptides and peptide derivatives have been extensively employed for constructing multifunctional nanotheranostics since they exhibit chemical versatility and enable to specically recognize other biomacromolecules. [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] In particular, conjugation of nanoparticles with tumor-homing peptides and/or therapeutic peptides can generate novel nanotheranostics for highly sensitive tumor imaging and effective tumor-targeted therapy. For example, Ruoslahti and coauthors have been developed a theranostic nanosystem, which consists of iron oxide nanoworms conjugated with a composite peptide with proapoptotic domain (i.e., therapy motif) and cell surface p32 protein binding domain (i.e., tumor-homing motif).…”