Multi-harmonic imaging in the second near-infrared window of nanoparticle-labeled stem cells as effective monitoring tool in tissue depth

In order to assess the therapeutic potential of cell-based strategies, it is of paramount importance to elaborate and validate new tools for monitoring the behavior of injected cells in terms of tissue dissemination and engraftment properties. Here, we apply Bismuth Ferrite harmonic nanoparticles (BFO HNPs) to in vitro expanded human skeletal muscle-derived stem cells (hMuStem cells), an attractive therapeutic avenue for patients suffering from Duchenne Muscular Dystrophy (DMD). We demonstrate the possibility of stem cell labeling with HNPs. We also show that the simultaneous acquisition of Second and Third Harmonic Generation (SHG and THG) from BFO HNPs helps separating their response from tissue background, with a net increase in imaging selectivity which could be particularly important in pathologic context that is defined by a highly remodelling tissue. We demonstrate the possibility of identifying