Sericin-based gadolinium nanoparticles as synergistically enhancing contrast agents for pH-responsive and tumor targeting magnetic resonance imaging

Abstract

It is of great significance to develop gadolinium (Gd) contrast agents (CAs) for pH-responsive and tumor targeting magnetic resonance imaging (MRI). Silkworm sericin (SS) is a natural biomacromolecule from silkworm cocoon with good biocompatibility, biodegradability, and a variety of biological activities. Here, sericin was covalently cross-linked with gadolinium acetate (GAH) via Schiff's base reaction, and then blended with gadolinium chloride (GdCl3) through electrostatic adsorption to yield SS@GAH-GdCl3 nanoparticles. Zeta potential showed SS@GAH-GdCl3 could respond pH change naturally, and freely realize the transition from negative surface potential in pH 7.5 to positive surface potential in pH 5.8. The T1 weighted MR images in solution indicated that SS@GAH-GdCl3 has higher T1 relaxivity in pH 5.8 than that in pH 7.4, and magnevist under 3.0 T magnetic field. Further, the T1 weighted MR images in vivo suggested that SS@GAH-GdCl3 could target tumors and accumulate around tumor tissues to achieve MR imaging on the tumor up to 2 h. Moreover, SS@GAH-GdCl3 is stable without any leakage of gadolinium ions. SS@GAH-GdCl3 is cytocompatible and does not cause hemolysis, inflammation, tissue damage, and the change of serum biochemical indicators and body weight in vivo. SS@GAH-GdCl3 has exhibited great potentials as a high-performance GdCA for pH-responsive and tumor targeting MRI.