Nanofactory for metabolic and chemodynamic therapy: pro-tumor lactate trapping and anti-tumor ROS transition

Journal of Nanobiotechnology

Haiqing Dong¹  Yuge Zhao²  Jingjing Gu²  Ying Liu²  Yongyong Li²  Gaowei Chong²  Ruiqing He²  Tingting Zhang²  Jie Zang²  Dailin Xu²  Shuangrong Ruan²  Yan Yang²  Yushan Yang²  Xiao Zheng² 

[1] Shanghai East hospital, School of Medicine, Tongji University, 200092, Shanghai, China;Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, 200092, Shanghai, China;

关键词: Lactate;    Immunosuppressive tumor microenvironment;    Immunogenic cell death;    Chemodynamic therapy;   

DOI  :  10.1186/s12951-021-01169-9

来源: Springer

【 摘 要 】

Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.Graphical Abstract

【 授权许可】

CC BY