Department of Chemistry, University of Liverpool, Oxford Street, Liverpool L69 7ZD, U.K.
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K.
ACS Appl Mater Interfaces. 2020 Jun 24;12(25):27930-27939. doi: 10.1021/acsami.0c03857. Epub 2020 Jun 12.
Noninvasive bioimaging techniques are critical for assessing the biodistribution of cellular therapies longitudinally. Among them, photoacoustic imaging (PAI) can generate high-resolution images with a tissue penetration depth of ∼4 cm. However, it is essential and still highly challenging to develop stable and efficient near-infrared (NIR) probes with low toxicity for PAI. We report here the preparation and use of perylene diimide derivative (PDI) with NIR absorbance (around 700 nm) as nanoprobes for tracking mesenchymal stromal cells (MSCs) in mice. Employing an in-house synthesized star hyperbranched polymer as a stabilizer is the key to the formation of stable PDI nanoparticles with low toxicity and high uptake by the MSCs. The PDI nanoparticles remain within the MSCs as demonstrated by in vitro and in vivo assessments. The PDI-labeled MSCs injected subcutaneously on the flanks of the mice are clearly visualized with PAI up to 11 days postadministration. Furthermore, bioluminescence imaging of PDI-labeled luciferase-expressing MSCs confirms that the administered cells remain viable for the duration of the experiment. These PDI nanoprobes thus have good potential for tracking administered cells in vivo using PAI.
非侵入性生物成像技术对于长期评估细胞疗法的生物分布至关重要。在这些技术中，光声成像（PAI）可以生成具有约 4 厘米组织穿透深度的高分辨率图像。然而，开发具有低毒性的稳定且高效的近红外（NIR）探针对于 PAI 仍然是必要的，并且极具挑战性。我们在此报告了具有 NIR 吸收（约 700nm）的苝二酰亚胺衍生物（PDI）作为纳米探针用于追踪小鼠中的间充质基质细胞（MSCs）的制备和使用。使用内部合成的星形超支化聚合物作为稳定剂是形成具有低毒性和高摄取率的稳定 PDI 纳米颗粒的关键。体外和体内评估表明，PDI 纳米颗粒仍保留在 MSCs 内。在给药后 11 天内，通过 PAI 可清晰地观察到注射到小鼠侧腹皮下的 PDI 标记 MSC。此外，PDI 标记的表达荧光素酶的 MSC 的生物发光成像证实，在实验过程中，给予的细胞仍然存活。因此，这些 PDI 纳米探针具有使用 PAI 体内追踪给予细胞的良好潜力。
