CT/bioluminescence dual-modal imaging tracking of stem cells labeled with Au@PEI@PEG nanotracers and RfLuc in nintedanib-assisted pulmonary fibrosis therapy

Abstract

Mesenchymal stem cells (MSCs) are promising in idiopathic pulmonary fibrosis (IPF) therapy. However, low survival rate and ambiguous behavior of MSCs after transplantation impede their clinical translation. To this end, we have developed a new strategy to improve the survival rate and monitor the behavior of the transplanted MSCs simultaneously. In our strategy, nintedanib, a tyrosine kinase inhibitor, is employed to protect the human MSCs (hMSCs) from excessive oxidative stress responses and inflammatory environment in the damaged lung. Moreover, by labeling of the transplanted hMSCs with a computed tomography (CT) nanotracer, Au nanoparticles functionalized with polyethylenimine (PEI) and polyethylene glycol (PEG) (Au@PEI@PEG), in combination with red-emitting firefly luciferase (RfLuc), in vivo CT/bioluminescence (BL) dual-modal imaging tracking of the location, distribution, and survival of the transplanted hMSCs in presence of nintedanib were achieved, which facilitates the profound understanding of the role the stem cells play in IPF therapy.