Development and in vitro evaluation of Silica-based iron oxide particles suitable for clinical application of cellular imaging with MRI

Introduction: Magnetic Resonance Imaging (MRI) can be used for non-invasive monitoring after liver cell transplantation (LCT), but clinical applicable micron-sized particles are not available. Aim of this study was the development a new class of micron-sized particles for cellular imaging based on clinical applicable materials.

Material and Methods: We developed silica-based particles (1.18µm) with different surface modifications: positively charged Poly-L-Lysin, neutral Streptavidin, and negative COOH-groups. Huh7-cells, primary rat hepatocytes, and primary human hepatocytes were used for in vitro evaluation. Cellular uptake mechanisms were investigated by inhibiting endocytosis using hypothermia (4°C) or culture medium supplemented with NaN3. Phantom studies were performed using a 3.0T whole body scanner. T2 maps were generated to quantify the amount of incorporated particles. Transaminase leakage was measured to investigate possible adverse effects of the particles.

Results: Cell labeling with Poly-L-Lysin particles produced an iron load of approximately 35pg iron/cell. COOH-coupled particles lead to about 22pg iron/cell, Streptavidin-particles achieved 6pg iron/cell. Treatment with endocytosis inhibitors caused no significant differences in particle uptake. Cells labeled with Poly-L-Lysin-particles were detectable from a cluster of at least 5,000 cells, whereas detection threshold for COOH- and Streptavidin-labeled cells were 10,000 and 25,000 cells, respectively. Effects on transaminase leakage were similarly low for all particles.

Discussion: We showed that efficient cell labeling with the new Silica-based particles is possible through passive uptake without negative effects on the labeled cells. Differently labeled cell clusters could be detected and quantified with clinical MRI. The different particle surface modifications reveal the opportunity to create multifunctional theranostic agents for diagnostic imaging, drug delivery or therapeutic monitoring.

MPIO - MRI - iron oxide particle - liver cell transplantation