SOD-Functionalized gold nanoparticles as ROS scavenger and CT contrast agent for protection and imaging tracking of mesenchymal stem cells in Idiopathic pulmonary fibrosis treatment

Development of functionalized nanoplatforms to simultaneously facilitate imaging tracking of transplanted stem cells and enhance their therapeutic efficacy through weakening oxidative stress damage has been a challenge in stem cell-based therapy. Herein, superoxide dismutase (SOD)-engineered gold nanoparticles (AuNPs), SOD@Au NS, was developed for collectively acting as a reactive oxygen species (ROS) scavenger and a computed tomography (CT) contrast agent for simultaneous protection and imaging tracking of mesenchymal stem cells (MSCs) in idiopathic pulmonary fibrosis (IPF) therapy. In this strategy, SOD, a key antioxidant enzyme that detoxifies intracellular ROS, was modified on the surface of AuNPs and then encapsulated into polyphosphazene nanospheres to overcome the poor cell membrane penetration and chemical stability of SOD, thereby promoting the survival of MSCs in a harsh inflammatory microenvironment by ROS elimination. What's more, SOD@Au NS where the assembly of an AuNP payload in a polyphosphazene core provides strong contrast enhancement in CT imaging owing to the dense packing of AuNP. After cellular uptake of SOD@Au NS, the labeled MSCs could be detected by CT technology, achieving continuous monitoring of the distribution and migration of MSCs for 18 days after transplantation in the IPF model mouse. Furthermore, we evaluated the long-term metabolism and safety of SOD@Au NS following transplantation of the stem cells into the alveolar interstitium. Consequently, this work may provide a novel insight into the development of safe and effective strategies to trace and protect transplanted stem cells, thus facilitating the subsequent preclinical research and clinical translation of stem cellbased IPF treatment.

Automated summary

The development of functionalized nanoplatforms for imaging tracking and therapeutic enhancement of stem cells in stem cell-based therapy is challenging. In this study, superoxide dismutase (SOD)-engineered gold nanoparticles (AuNPs) were developed for oxidative stress damage mitigation and computed tomography (CT) imaging tracking of mesenchymal stem cells (MSCs) in idiopathic pulmonary fibrosis (IPF) therapy. The SOD@Au NS, composed of SOD modified on the surface of AuNPs and encapsulated into polyphosphazene nanospheres, promoted MSC survival by eliminating reactive oxygen species (ROS) in the inflammatory microenvironment and provided strong contrast enhancement in CT imaging. The labeled MSCs could be detected by CT technology for continuous monitoring after transplantation, enabling the development of safe and effective strategies for stem cell-based IPF treatment.