CT/MR Dual-Modality Imaging Tracking of Mesenchymal Stem Cells Labeled with a Au/GdNC@SiO₂ Nanotracer in Pulmonary Fibrosis

Abstract

Mesenchymal stem cells (MSCs) have shown potential as an innovative treatment for pulmonary fibrosis (PF), due to their capability to ameliorate the inflammation and moderate the deterioration of PF. The fate of the stem cells transplanted into the lung, including survival, migration, homing, and functions, however, has not been fully understood yet. In this paper, we report the development of a computed tomography/ magnetic resonance (CT/MR) dual-modal nanotracer, gold/ gadolinium nanoclusters overcoated with a silica shell (Au/ GdNC@SiO 2 ), for noninvasive labeling and tracking of the transplanted human MSCs (hMSCs) in a PF model. The Au/ GdNC@SiO 2 nanotracer exhibits good colloidal and chemical stability, high biocompatibility, enhanced longitudinal MR relaxivity, and superior X-ray attenuation property. The hMSCs can be effectively labeled with Au/GdNC@SiO 2 , resulting in a significantly increased cellular CT/MR imaging contrast, without any obvious adverse effect on the function, including proliferation and differentiation of the labeled stem cells. Moreover, by using the Au/GdNC@SiO 2 nanotracer, the hMSCs transplanted in the lung can be tracked for 7 d via in vivo CT/MR dual-modality imaging. This work may provide an insight into the role the transplanted hMSCs play in PF therapy, thus promoting the stem cell-based regenerative medicine.

In vivo CT imaging tracking of stem cells labeled with Au nanoparticles

“…In a recent work, we constructed a novel type of multifunctional NPs, gold/gadolinium nanoclusters coated with a silica shell (Au/GdNC@SiO 2 ), for CT/MR dual-modal imaging tracking of hMSCs in a PF model mouse. 38 The hMSCs labeled with Au/GdNC@SiO 2 exhibited significantly enhanced cellular CT/MR imaging effect because of the silica coating on Au/GdNC surface. Since the detection sensitivity of MRI is much higher than that of CT imaging, at the same concentration of the NPs, MRI signals were much more easily observed than CT signals.…”

“…In recent years, various types of hybrid AuNPs have been developed for CT‐based multimodal imaging tracking of stem cells. In a recent work, we constructed a novel type of multifunctional NPs, gold/gadolinium nanoclusters coated with a silica shell (Au/GdNC@SiO 2 ), for CT/MR dual‐modal imaging tracking of hMSCs in a PF model mouse 38 . The hMSCs labeled with Au/GdNC@SiO 2 exhibited significantly enhanced cellular CT/MR imaging effect because of the silica coating on Au/GdNC surface.…”

“…The size of AuNPs imposes important influences on their X-ray attenuation, cellular uptake, and biocompatibility. Xu et al investigated the CT attenuation of AuNPs with different sizes (4,20,38, and 60 nm), and found that the smaller AuNPs showed greater X-ray attenuation than the larger ones under the same Au content, attributing to that smaller AuNPs has larger surface area and more dramatic X-ray attenuation (Figure 2A). 27 Nevertheless, the CT imaging effect of the labeled cells not only depends on the intrinsic CT attenuation property of the contrast agents, but is also correlated with the content of contrast agents taken up by cells.…”

Cell membrane camouflaged biomimetic nanoparticles: Focusing on tumor theranostics

“…In recent, iodinated agents are considered as the clinically safe contrast agent but sometimes cause serious side effects due to their high permeability and viscosity [ 138 , 139 ]. In addition, CT imaging has a high spatial resolution for cell level quantification, but the sensitivity is extremely limited [ 140 ]. Over the past years, with the rapid development of nanotechnology, various nanomaterials have been introduced into CT applications, especially the biomimetic nano-system used as the advanced contrast agent to not only reduce the immune clearance and the toxic side effects, but also enhance target delivery to the tumor [ 141 ].…”

Nanotechnology-Assisted Cell Tracking

“…Indeed, the use of a combination of two or more chemical elements to be traced by means of different imaging techniques, known as the multi-labeling approach, represents a way to overcome the imaging detection limits of a specific technique. As some examples, inorganic gold NPs with red-emitting firefly luciferase (RfLuc)-based bioluminescence (BL) tags [43] and inorganic NPs with gold and gadolinium elements [44] have been developed for the noninvasive labeling and tracking of human mesenchymal stem cells (hMSCs) in a mouse model of pulmonary disease. Specifically, multimodal imaging with CT, MRI and BL was successfully adopted to characterize the in vivo migration, homing, functions, and survival of transplanted hMSCs, giving further insight for the treatment of pulmonary fibrosis.…”