Loading of metal isotope-containing intercalators for mass cytometry-based high-throughput quantitation of exosome uptake at the single-cell level
Loading of metal isotope-containing intercalators for mass cytometry-based high-throughput quantitation of exosome uptake at the single-cell level
复制标题
加载含金属同位素的嵌入剂，用于基于质量流式细胞术的单细胞水平外泌体摄取的高通量定量
DOI：
10.1016/j.biomaterials.2020.120152
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发表时间：
2020
期刊：
影响因子：
14
通讯作者：
Liu Jinbao
中科院分区：
文献类型：
--
作者：
Wang Jinheng;Tu Chenggong;Zhang Hui;Zhang Jian;Feng Yueyuan;Deng Yangyang;Huo Yongliang;Xie Maobin;Yang Bin;Zhou Miao;Liu Jinbao
纳米大小的外泌体作为细胞与细胞之间的通讯器和多功能药物载体正在被广泛研究。这些外泌体的生物分布的表征对于评价其生物学功能和药物递送功效是必不可少的。然而，目前用于外来体追踪的技术依赖于荧光，并且由于可用通道的数量有限和光谱溢出而具有低通量的缺点。在这里，我们报道了一种工程方法的开发，该方法涉及将含金属同位素的嵌入剂装载到外泌体中，以在单细胞水平上量化外泌体摄取。我们证明，质谱细胞计数结合高度多变量的细胞表型，使高通量鉴定外来体的体内命运。受这些对细胞分布的见解的启发，我们优化了基于外泌体的药物递送的给药方法，验证了这些外泌体在乳腺癌小鼠模型中的抗癌功效。在单细胞水平上评估外来体在体内的命运提供了对外来体在体内的功能的有价值的见解，并促进了基于外来体的治疗的改进。
Nanometer-sized exosomes are being widely studied as cell-to-cell communicators and versatile drug vehicles. Characterizations of the biodistribution of these exosomes are essential for the evaluation of their biological functions and drug delivery efficacy. However, current technologies for exosome tracking rely on fluorescence and have the disadvantages of being low throughput due to the limited number of available channels and spectral spillover. Here, we reported the development of an engineering approach that involves loading of metal isotope-containing intercalators into exosomes to quantify exosome uptake at the single-cell level. We demonstrate that mass cytometry in conjunction with highly multivariate cellular phenotyping enables high-throughput identification of the in vivo fate of exosomes. Inspired by these insights into cellular distribution, we optimized the administration methods for exosome-based drug delivery, verifying the anticancer efficacy of these exosomes in a mouse model of breast cancer. The evaluation of exosome's fate in vivo at the single-cell level provides valuable insights into the functions of exosomes in vivo and facilitates the improvement of exosome-based therapy.