Organic Semiconducting Polymer Nanoparticles for Photoacoustic Labelling and Tracking of Stem Cells in the Second Near-Infrared Window.

Photoacoustic (PA) imaging and tracking of stem cells plays an important role in the real-time assessment of cell-based therapies. Nevertheless, the limitations of conventional inorganic PA contrast agents and the narrow range of the excitation wavelength in the first near-infrared (NIR-I) window hamper the applications of PA imaging in living subjects. Herein we report the design and synthesis of a second near-infrared (NIR-II) absorptive organic semiconducting polymer (OSP)-based nanoprobe (OSPN+) for PA imaging and tracking of stem cells. Comparison studies in biological tissue showed that NIR-II light excited PA imaging of the OSPN+ had significantly higher signal-to-noise ratio (SNR) than NIR-I light excited PA imaging, thereby demonstrating the superiority of the OSPN+ for deep tissue imaging. With good biocompatibility, appropriate size, and optimized surface property, the OSPN+ showed enhanced cellular uptake for highly efficient PA labelling of stem cells. In vivo investigations revealed significant NIR-II PA contrast enhancement of the transplanted OSPN+-labelled human mesenchymal stem cells (hMSCs) by 40.6- and 21.7-fold in subcutaneous and brain imaging, respectively, compared with unlabelled cases. Our work demonstrates a class of OSP-based nanomaterials for NIR-II PA stem cell imaging to facilitate a better understanding and evaluation of stem cell-based therapies.