BSA directed-synthesis of biocompatible Fe3O4 nanoparticles for dual-modal T1 and T2 MR imaging in vivo

Abstract

High-performance magnetic resonance (MR) imaging contrast agents are the key to reliable and accurate diagnosis of diseases using the MR imaging technique. In particular, dual-modal MR imaging nanoprobes that integrated the advantages of a high contrast effect and impressive sensitivity of T₁- and T₂-weighted MR imaging, respectively, have attracted increasing attention in recent years. However, the current methods for the fabrication of the dual-modal MR imaging nanoprobes suffer from a tedious synthesis procedure, harsh synthesis condition and ambiguous toxicity, strongly hindering their clinic transformation. Herein, we proposed a biomineralization approach for the fabrication of bovine serum albumin (BSA)–Fe₃O₄ nanoparticles with undoubted biosafety and robust T₁ and T₂ MR imaging ability in a facile way under mild conditions. BSA not only served as a template to control the growth of nanocrystal, but also enabled the favorable water solubility of the nanoprobe. The outstanding biocompatibility of BSA–Fe₃O₄ nanoparticles was proven by systematic in vitro and in vivo toxicity assessments, and dual-modal T₁ and T₂ MR imaging in vivo was achieved successfully. In addition, the nanoprobe was successfully applied for in vivo MR imaging of liver with a broad time window, and the metabolic investigation of BSA–Fe₃O₄ nanoparticles revealed that they could be eliminated from the body, ensuring a negligible adverse effect. The proposed biomineralization approach opens a new way for the fabrication of dual-modal MR contrast imaging nanoprobe with undoubted biosafety, and other functional proteins also exhibit great potential for the fabrication of dual-modal MR contrast imaging nanoprobe with specific functions with respect to biomineralization.