Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy
Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy
复制标题
远程控制富含光敏剂的中性粒细胞用于癌症免疫治疗
DOI：
10.1016/j.celrep.2020.108499
复制
发表时间：
2020-12-15
期刊：
影响因子：
8.8
通讯作者：
Li, Yongyong
中科院分区：
文献类型：
--
作者：
Li, Yan;Han, Yi;Li, Yongyong
通过引入人工活性氧物种(ROS)的产生机制，设计了一种生物/非生物整合，通过遥控途径人工增强中性粒细胞的ROS效应机制，以提高其抗肿瘤效果。具体地说，光敏剂Ce6是由白蛋白BSA纳米包装的，以实现与中性粒细胞(NE)的生物相容性和高效整合。与Ce6纳米制剂相比，将工程NE重新注入4T1荷瘤小鼠导致了更多的Ce6在肿瘤中的积聚。在积聚的高峰期，肿瘤照射激活嵌入的Ce6，以产生ROS和形成NETsis。由于ROS增强的细胞溶解作用，4T1肿瘤的生长受到显著抑制。这种光控过程在很大程度上避免了在目前的细胞治疗中经常观察到的非靶点效应。该策略直接生成具有时空精度的ROS效应分子。这种工程方法能够增强免疫细胞的天然能力，而不受肿瘤微环境的影响。
By incorporating an artificial reactive oxygen species (ROS) generation mechanism, a biotic/abiotic integration is designed to improve the anti-tumor effect of neutrophils by artificially potentiating their ROS effector mechanism in a remotely controlled route. Specifically, the photosensitizer Ce6 is nano-packaged by the albumin BSA to achieve biocompatible and efficient integration with neutrophils (NEs). Reinfusion of the engineered NEs into 4T1 tumor-bearing mice led to more Ce6 accumulation in tumors relative to Ce6 nanoformulation. At the peak of accumulation, tumor illumination activates the embedded Ce6 for ROS generation and NETosis formation. Because of the ROS-intensified cytolytic effect, the growth of 4T1 tumors is inhibited significantly. The photo-controlled process largely avoids the off-target effects observed frequently in current cell therapies. The strategy directly generates ROS effector molecules with spatiotemporal precision. This engineering approach is able to potentiate the native capacity of immune cells independent of the tumor microenvironment.