Department of Bioengineering, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA.
Biomater Sci. 2019 Apr 23;7(5):2123-2133. doi: 10.1039/c8bm01448e.
Particle-based systems provide a capability for the delivery of imaging and/or therapeutic payloads. We have engineered constructs derived from erythrocytes, and doped with the FDA-approved near infrared dye, indocyanine green (ICG). We refer to these optical particles as NIR erythrocyte-mimicking transducers (NETs). A particular feature of NETs is that their diameters can be tuned from micron- to nano-scale. Herein, we investigated the effects of micron- (≈2.6 μm diameter), and nano- (≈145 nm diameter) sized NETs on their biodistribution, and evaluated their acute toxicity in healthy Swiss Webster mice. Following tail vein injection of free ICG and NETs, animals were euthanized at various time points up to 48 hours. Fluorescence analysis of blood showed that nearly 11% of the injected amount of nano-sized NETs (nNETs) remained in blood at 48 hours post-injection as compared to ≈5% for micron-sized NETs (μNETs). Similarly, at this time point, higher levels of nNETs were present in various organs including the lungs, liver, and spleen. Histological analyses of various organs, extracted at 24 hours post-injection of NETs, did not show pathological alterations. Serum biochemistry profiles, in general, did not show elevated levels of the various analyzed biomarkers associated with liver and kidney functions. Values of various hematological profiles remained within the normal ranges following the administration of μNETs and nNETs. Results of this study suggest that erythrocyte-derived particles can potentially provide a non-toxic platform for delivery of ICG.
基于粒子的系统提供了一种传递成像和/或治疗有效载荷的能力。我们已经设计了源自红细胞的构建体，并掺杂了经美国食品和药物管理局批准的近红外染料吲哚菁绿（ICG）。我们将这些光学粒子称为近红外红细胞模拟换能器（NETs）。NETs 的一个特别之处是它们的直径可以从微米到纳米级调节。在此，我们研究了微米（≈2.6μm 直径）和纳米（≈145nm 直径）尺寸的 NETs 对其生物分布的影响，并在健康的瑞士 Webster 小鼠中评估了它们的急性毒性。在尾静脉注射游离 ICG 和 NETs 后，动物在 48 小时内的不同时间点被安乐死。血液荧光分析显示，与微米大小的 NETs（μNETs）相比，纳米大小的 NETs（nNETs）在注射后 48 小时内仍有约 11%的注射量留在血液中。同样，在这个时间点，nNETs 在包括肺、肝和脾在内的各种器官中的含量更高。在注射 NETs 24 小时后提取的各种器官的组织学分析未显示出病理改变。一般来说，血清生化谱没有显示与肝肾功能相关的各种分析生物标志物的升高水平。在给予μNETs 和 nNETs 后，各种血液学谱的值仍保持在正常范围内。这项研究的结果表明，红细胞衍生的粒子有可能为 ICG 的传递提供一种无毒的平台。
