Stem cell-mediated delivery of SPIO-loaded gold nanoparticles for the theranosis of liver injury and hepatocellular carcinoma

The treatment of liver injuries or hepatocellular carcinoma (HCC) has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system. As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@ AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@ AuNP is a non-toxic magnetic resonance (MR)-active contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@ AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MR imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@ AuNP-loaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@ AuNP-loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.