A novel formulation strategy was proposed herein for Gd-based macromolecular MRI contrast agents (Gd-mCAs), which may significantly reduce Gd( III) retention but maintain sufficient imaging contrast. Accumulation of nano-scale contrast agents in body tissues potentially induces adverse effects associated with free Gd( III) ion release from the nano-scale system, such as nephrogenic systemic fibrosis and gadolinium deposition in the brain tissue.