Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Physiology, Biophysics, & Systems Biology Graduate Program, Weill Cornell Medical College, Cornell University, New York, New York, United States of America.
PLoS One. 2020 May 6;15(5):e0226791. doi: 10.1371/journal.pone.0226791. eCollection 2020.
Over the past two decades, measurements of carbon nanotube toxicity and biodistribution have yielded a wide range of results. Properties such as nanotube type (single-walled vs. multi-walled), purity, length, aggregation state, and functionalization, as well as route of administration, greatly affect both the biocompatibility and biodistribution of carbon nanotubes. These differences suggest that generalizable conclusions may be elusive and that studies must be material- and application-specific. Here, we assess the short- and long-term biodistribution and biocompatibility of a single-chirality DNA-encapsulated single-walled carbon nanotube complex upon intravenous administration that was previously shown to function as an in-vivo reporter of endolysosomal lipid accumulation. Regarding biodistribution and fate, we found bulk specificity to the liver and >90% signal attenuation by 14 days in mice. Using near-infrared hyperspectral microscopy to measure single nanotubes, we found low-level, long-term persistence in organs such as the heart, liver, lung, kidney, and spleen. Measurements of histology, animal weight, complete blood count; biomarkers of organ function all suggest short- and long-term biocompatibility. This work suggests that carbon nanotubes can be used as preclinical research tools in-vivo without affecting acute or long-term health.
在过去的二十年中，对碳纳米管毒性和生物分布的测量产生了广泛的结果。诸如纳米管类型（单壁与多壁）、纯度、长度、聚集状态和功能化以及给药途径等性质极大地影响了碳纳米管的生物相容性和生物分布。这些差异表明，可能难以得出普遍的结论，并且研究必须针对特定的材料和应用。在这里，我们评估了先前被证明作为内溶酶体脂质积累的体内报告器的单手性 DNA 包封单壁碳纳米管复合物静脉内给药后的短期和长期生物分布和生物相容性。关于生物分布和命运，我们发现该复合物在小鼠体内具有肝脏的整体特异性，并且在 14 天内信号衰减超过 90％。使用近红外高光谱显微镜测量单根纳米管，我们发现低水平的长期在心脏、肝脏、肺、肾脏和脾脏等器官中存在。组织学测量、动物体重、全血细胞计数；器官功能的生物标志物均表明短期和长期的生物相容性。这项工作表明，碳纳米管可以在不影响急性或长期健康的情况下用作体内临床前研究工具。
