Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy
Yan Li,
Yi Han,
Runping Su,
Yiqiong Liu,
Gaowei Chong,
Dailin Xu,
Ruiqing He,
Ying Liu,
Haiqing Dong,
Donglu Shi,
Yongyong Li
Affiliations
Yan Li
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China; Corresponding author
Yi Han
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Runping Su
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Yiqiong Liu
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Gaowei Chong
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Dailin Xu
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Ruiqing He
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Ying Liu
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Haiqing Dong
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China
Donglu Shi
The Materials Science & Engineering Program, Department of Mechanical & Materials Engineering, College of Engineering & Applied Science, University of Cincinnati, Cincinnati, OH 45221, USA
Yongyong Li
Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P.R. China; Corresponding author
Summary: 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.
