Increasing the Efficacy of Gold Nanorod Uptake in Stem Cell-Derived Therapeutic Cells: Implications for Stem Cell Labeling and Optical Coherence Tomography Imaging
Increasing the Efficacy of Gold Nanorod Uptake in Stem Cell-Derived Therapeutic Cells: Implications for Stem Cell Labeling and Optical Coherence Tomography Imaging
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DOI：
10.1021/acsanm.2c00958
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发表时间：
2022-05
影响因子：
5.9
通讯作者：
Grant W Marquart;Jonathan Stoddard;Karen Kinnison;F. Zhou;Richard Hugo;R. Ryals;Scott A. Shubert
中科院分区：
文献类型：
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作者：
Grant W Marquart;Jonathan Stoddard;Karen Kinnison;F. Zhou;Richard Hugo;R. Ryals;Scott A. Shubert
用作光学相干断层扫描（OCT）成像和干细胞标记剂的安全纳米材料的进步，用于纵向视觉跟踪治疗性视网膜干细胞以研究其迁移、存活率和功效，但面临着不稳定性、细胞内聚集、低摄取和细胞毒性的挑战。在这里，我们描述了一系列可以解决这些问题的混合脂质涂层金纳米棒（AuNR）。这些纳米材料是通过层层组装方法制成的，并将它们在生物介质中的稳定性、机制、吸收效率和毒性与具有 5 nm 介孔二氧化硅 (mSiO2) 聚合物涂层的市售 AuNR 进行了比较。这些纳米材料可以用作干细胞标记和 OCT 成像剂，因为它们吸收远离生物组织的近红外 (NIR) 区域。尽管 AuNR 的两种亚型均被视网膜色素上皮细胞、神经祖细胞和幼仓鼠肾细胞吸收，但带轻微负电荷的混合脂质包被的 AuNR 在生物介质和细胞质内的聚集程度极低（约 3000 AuNR/细胞），对细胞健康的影响也极小。用细胞穿透肽修饰的混合脂质包被 AuNR 的毒理学影响最小，细胞活力 >92%。相比之下，具有 5 nm mSiO2 聚合物涂层的更“粘”的 AuNR 在生物介质和细胞质内显示出显着的聚集，并且由于其高正表面电荷（35+ mV），AuNR 的吸收低于预期（约 5400 个 AuNR/细胞）。总的来说，我们已经证明，混合脂质包被的 AuNR 在远离生物组织的 NIR-II 区域吸收，具有经过调整的表面化学，可以标记治疗衍生的干细胞，同时最大限度地减少聚集和对细胞健康的影响，并增强 OCT 成像应用的吸收。
The advancement of safe nanomaterials for use as optical coherence tomography (OCT) imaging and stem cell-labeling agents to longitudinally visually track therapeutic derived retinal stem cells to study their migration, survival rate, and efficacy is challenged by instability, intracellular aggregation, low uptake, and cytotoxicity. Here, we describe a series of hybrid lipid-coated gold nanorods (AuNRs) that could solve these issues. These nanomaterials were made via a layer-by-layer assembly approach, and their stability in biological media, mechanism, efficiency of uptake, and toxicity were compared with a commercially available set of AuNRs with a 5 nm mesoporous silica (mSiO2)-polymer coating. These nanomaterials can serve as stem cell labeling and OCT imaging agents because they absorb in the near-infrared (NIR) region away from biological tissues. Although both subtypes of AuNRs were taken up by retinal pigment epithelial, neural progenitor, and baby hamster kidney cells, slightly negatively charged hybrid lipid-coated AuNRs had minimal aggregation in biological media and within the cytoplasm of cells (∼3000 AuNRs/cell) as well as minimal impact on cell health. Hybrid lipid-coated AuNRs modified with cell-penetrating peptides had the least toxicological impact, with >92% cell viability. In contrast, the more “sticky” AuNRs with a 5 nm mSiO2-polymer coating showed significant aggregation in biological media and within the cytoplasm with lower-than-expected uptake of AuNRs (∼5400 of AuNRs/cell) given their highly positive surface charge (35+ mV). Collectively, we have demonstrated that hybrid lipid-coated AuNRs, which absorb in the NIR-II region away from biological tissues, with tuned surface chemistry can label therapeutic derived stem cells with minimal aggregation and impact on cell health as well as enhance uptake for OCT imaging applications.