A unique nanogel-based platform for enhanced dual mode tumor MR/CT imaging

Abstract

We develop a convenient approach to loading both gold nanoparticles (AuNPs) and gadolinium (Gd) within alginate nanogels (AG NGs) for enhanced tumor dual-modal MR/CT imaging applications. In this study, polyethyleneimine (PEI) partially modified with polyethylene glycol (PEG) was used to entrap AuNPs and load gadolinium via chelation. The formed PEI-Au-Gd NPs were used as a crosslinker to crosslink AG NGs with activated carboxyl groups obtained through a double emulsion process. The formed hybrid NGs (AG/PEI-Au-Gd NGs) having a size of 83 ± 21 nm exhibit excellent colloidal stability in aqueous solution and good cytocompatibility in the studied concentration range. In particular, the AG/PEI-Au-Gd NGs exhibit a higher r₁ relaxivity (9.16 mM⁻¹ s⁻¹) than acetylated PEI-Au-Gd NPs (PEI.Ac-Au-Gd NPs) and a clinical MR contrast agent and a greater X-ray attenuation performance than conventional iodinated CT contrast agents (e.g., Omnipaque), and they can be more significantly taken up by cancer cells than PEI.Ac-Au-Gd NPs. Furthermore, the AG/PEI-Au-Gd NGs enable effective dual mode MR/CT imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Strikingly, the AG/PEI-Au-Gd NGs exhibit a much better dual-modal MR/CT imaging performance than PEI.Ac-Au-Gd NPs and clinical CT or MR agents in in vivo tumor imaging. The developed AG/PEI-Au-Gd NGs with good biosafety confirmed by histological examinations may be potentially employed as an efficient contrast agent for enhanced dual-modal MR/CT imaging applications.