Photoacoustic Imaging of Embryonic Stem Cell‐Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles

Abstract

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have become promising tools to repair injured hearts. To achieve optimal outcomes, advanced molecular imaging methods are essential to accurately track these transplanted cells in the heart. In this study, it is demonstrated for the first time that a class of photoacoustic nanoparticles (PANPs) incorporating semiconducting polymers (SPs) as contrast agents can be used in the photoacoustic imaging (PAI) of transplanted hESC-CMs in living mouse hearts. This is achieved by virtue of two benefits of PANPs. First, strong photoacoustic (PA) signals and specific spectral features of SPs allow PAI to sensitively detect and distinguish a small number of PANP-labeled cells (2000) from background tissues. Second, the PANPs show a high efficiency for hESC-CM labeling without adverse effects on cell structure, function, and gene expression. Assisted by ultrasound imaging, the delivery and engraftment of hESC-CMs in living mouse hearts can be assessed by PANP-based PAI with high spatial resolution (≈100 µm). In summary, this study explores and validates a novel application of SPs as a PA contrast agent to track labeled cells with high sensitivity and accuracy in vivo, highlighting the advantages of integrating PAI and PANPs to advance cardiac regenerative therapies.

Accomplishments and challenges in stem cell imaging in vivo

“…Further, the administration of 5 Â 10 4 MSCs could be followed in mice for 14 days [97]. Similar results were reported using hESC-CMs in living mouse hearts labeled with semiconducting polymers that also absorb in the 700 nm range [98]. With this label, they also showed the detection limit to be 200 cells/mm 3 following subcutaneous injection.…”

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

“…In order to increase the image contrast when using this technique, nanoparticles have been successfully employed as contrast agent material (Calcagno et al, 2019). Qin et al (2018) recently reported the use of NPs composed by a semiconductor polymeric contrast agent (PCPDTBT) encapsulated in a FDA approved lipid-based copolymer (DSPE-PEG-Maleimide). NPs functionalized with cell-penetrating peptide (CPP) were able to target and label hESCs-derived cardiomyocytes (hECS-CM).…”

A Nanoprobe for Diagnosing and Mapping Lymphatic Metastasis of Tumor Using 3D Multispectral Optoacoustic Tomography Owing to Aggregation/Deaggregation Induced Spectral Change

“…Nevertheless, based on diffuse‐light‐based imaging, pure optical detection techniques have some limitations such as relatively low spatial resolution and penetration depth because of strong light scattering in deep tissue . On the other hand, optoacoustic (OA) imaging, also known as photoacoustic (PA) imaging, integrates the good contrast and high sensitivity attainable in optical imaging with the deep penetration and high resolution of ultrasound . With pulsed‐laser light illumination, the OA contrast agents (either endogenous or exogenous) undergo thermoelastic expansion, and produce ultrasound waves which are detected with an ultrasound detector.…”