Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy

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. [Display omitted] •The photosensitizer is nano-packaged by BSA to facilitate integration•Tumor accumulation is obtained by the inherent tumor-targeting ability of neutrophils•The cytolytic activity of neutrophils is intensified by artificial ROS generation•Intensified ROS generation can be mediated in a temporospatial manner Li et al. develop a biotic/abiotic integration mechanism to improve the cytolytic effect of neutrophils by incorporating a nano-photosensitizer in neutrophils. Through a direct synergistic effect of ROS generated by photo-activated nano-photosensitizers, the anti-tumor effect of neutrophils is improved significantly in a remotely controlled route.