Wang Jinheng, Tu Chenggong, Zhang Hui, Zhang Jian, Feng Yueyuan, Deng Yangyang, Huo Yongliang, Xie Maobin, Yang Bin, Zhou Miao, Liu Jinbao
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University, School of Basic Medical Sciences, Guangzhou Medical University, 510150, Guangzhou, China; Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, 510095, Guangzhou, China.
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University, School of Basic Medical Sciences, Guangzhou Medical University, 510150, Guangzhou, China.
Biomaterials. 2020 Oct;255:120152. doi: 10.1016/j.biomaterials.2020.120152. Epub 2020 May 27.
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.
纳米级外泌体作为细胞间通讯介质和多功能药物载体正受到广泛研究。这些外泌体生物分布的表征对于评估其生物学功能和药物递送效果至关重要。然而，当前用于外泌体追踪的技术依赖于荧光，并且由于可用通道数量有限和光谱溢出而存在通量低的缺点。在此，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加载到外泌体中，以在单细胞水平上量化外泌体摄取。我们证明，质谱流式细胞术与高度多变量的细胞表型分析相结合，能够高通量鉴定外泌体在体内的命运。受这些关于细胞分布的见解启发，我们优化了基于外泌体的药物递送的给药方法，在乳腺癌小鼠模型中验证了这些外泌体的抗癌功效。在单细胞水平上评估外泌体在体内的命运，为外泌体在体内的功能提供了有价值的见解，并有助于改进基于外泌体的治疗。
