Mesoporous Silica Nanoparticles as a Delivery System of Gadolinium for Effective Human Stem Cell Tracking

Abstract

The progress of using gadolinium (Gd)-based nanoparticles in cellular tracking lags behind that of superparamagnetic iron oxide (SPIO) nanoparticles in magnetic resonance imaging (MRI). Here, dual functional Gd-fluorescein isothiocyanate mesoporous silica nanoparticles (Gd-Dye@MSN) that possess green fluorescence and paramagnetism are developed in order to evaluate their potential as effective T1-enhancing trackers for human mesenchymal stem cells (hMSCs). hMSCs are labeled efficiently with Gd-Dye@MSN via endocytosis. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes, osteocytes, and chondrocytes, which can still be readily MRI detected. Imaging, with a clinical 1.5-T MRI system and a low incubation dosage of Gd, low detection cell numbers, and short incubation times is demonstrated on both loaded cells and hMSC-injected mouse brains. This study shows that the advantages of biocompatibility, durability, high internalizing efficiency, and pore architecture make MSNs an ideal vector of T1-agent for stem-cell tracking with MRI.

Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods

“…42 This work sought to answer two questions: (1) Can SiGNRloaded MSCs still differentiate? 43 and (2) Does the presence of SiGNRs induce any unintended differentiation? We were especially concerned that the SiGNRs might unintentionally transform MSCs into osteogenic cells as silicon-based structures have previously been show to induce such differentiation.…”

“…The next generation of this contrast agent may have a larger aspect ratio to induce longer red-shifted resonances. 56 Finally, we will dope Gd 3+ into the silica shell of the SiGNRs for T1 magnetic resonance imaging 43 to complement the PA mode for long-term monitoring of implanted MSCs with greater depth of penetration. Bmode imaging for visualization of the delivery catheter and the in vivo environment is complemented nicely by PA-mode that specifically enhances MSC signal.…”

Gadolinium3+-doped mesoporous silica nanoparticles as a potential magnetic resonance tracer for monitoring the migration of stem cells in vivo

“…8 The nanoparticles could remain in the cells for several days; for example, the cells prelabeled with nanoparticles for 7 days could still be detected by MRI. 21 Stem cells are functionally defined by their capacity for self-renewal and differentiation into multiple cell types. MSCs can differentiate into various types of cells under various conditions, such as adipocytes, osteocytes, chondrocytes, and neurons.…”

“…The mesoporous structure can hold paramagnetic gadolinium (Gd) ions, allowing easy water access to Gd ions and a high degree of interaction between Gd ions and water protons, which contribute to increasing MR signals. [16][17][18][19][20] Hsiao et al 21 first reported on an efficient stem cell-tracking media made by Gd-loaded mesoporous silica nanoparticles that did not affect cell viability or differentiation; this laid the foundation for future visual stem cell therapies using T 1 -weighted MRI with a Gd-based positive contrast agent instead of superparamagnetic iron oxide (SPIO). Additionally, monitoring the fate of transplanted cells in vivo is an increasingly indispensable part of assessing the nanoprobe as a cellular tracer; in particular, the combination of MR images with histological analysis provides for a more thorough investigation.…”

Nanoparticles and their potential for application in bone

“…Equally, mesoporous silica nanoparticles, either functionalized with different amounts of positively charged functional groups or with gadolinium, did not influence MSC differentiation, as confirmed by qualitative analyses after short-term exposure. 104,105 In addition to the effects on the differentiation potential, further MSC functions can be modulated by nanoparticles. Ferucarbotran particles with superparamagnetic properties were efficiently taken up by MSCs.…”