Gd-Chelated poly(propylene imine) dendrimers with densely organized maltose shells for enhanced MR imaging applications

Abstract

We report the design of the fourth generation poly(propylene imine) (PPI) glycodendrimers for magnetic resonance (MR) imaging applications. The glycodendrimers were designed to have a densely organized maltose shell (MAL DS) and several tetraazacyclododecane tetraacetic acid (DOTA) ligands that were attached to the periphery of the PPI dendrimers for Gd(III) chelation. We show that the formed MAL DS-modified PPI dendrimers possess good cytocompatibility and hemocompatibility in the studied concentration range. With the longitudinal relaxivity (r₁) of PPI-MAL DS-DOTA(Gd) (10.2 mM⁻¹ s⁻¹), which is 3.0 times higher than that of DOTA(Gd) (3.4 mM⁻¹ s⁻¹), the developed PPI-MAL DS-DOTA(Gd) nanocomplexes can be used as an efficient contrast agent for MR imaging of cancer cells in vitro, and animal aorta, renal artery, kidney, and bladder in vivo. Furthermore, tissue distribution studies show that the glycodendrimer/Gd complexes are metabolized and cleared out of the body at 48 h post injection. The developed PPI-MAL DS-DOTA(Gd) may be further functionalized for MR imaging of different biological systems.