Controlled synthesis of shell cross-linked magnetic micelles for efficient liver MR imaging

Abstract

In this paper, we report the fabrication, characterization and ex vivo bio-distribution of Rhodamine B-labeled shell cross-linked magnetic micelles (RhB-SCL-MMs) as a T₂-weighted magnetic resonance contrast agent. Three sizes of hybrid micelles (80, 130 and 180 nm) are synthesized and the size effects on the cytotoxicity and cell uptake in macrophage cells (RAW264.7) are evaluated. The ex vivo bio-distribution experiments confirm that the three sizes of RhB-SCL-MMs are mainly accumulated in the liver and spleen after intravenous injection, which suggests that the micelles could be used as an efficient MR contrast agent for liver imaging. In addition, no tissue toxicity is detected in tissue slice tests. The application of RhB-SCL-MMs of different sizes is demonstrated for magnetic resonance imaging (MRI) both in vitro and in vivo. A maximum r₂ value of 320.7 mM⁻¹ s⁻¹ is obtained for the RhB-SCL-MMs with the highest loading amount of magnetite, which is much higher than that of the well-known, liver-specific, T₂-weighted contrast agent Feridex (iron oxide, r₂ = 108 mM⁻¹ s⁻¹). The in vivo MRI studies show that the contrast enhancement of RhB-SCL-MMs in the liver is dependent on the diameter of the micelles, where the 130 nm RhB-SCL-MMs exhibit the most significant enhancement. In addition, the multifunctional nanoparticles present promising application potential in liver tumor MR imaging through enhanced permeability and retention (EPR) effect. Therefore, these kinds of iron oxide-based cross-linked micelles could be used as excellent, safe MR contrast agents for the diagnosis of liver diseases or cancers.