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

J Nanobiotechnology

Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, 200092, Shanghai, China.

Published: December 2021

AI Article Synopsis

  • Lactate contributes to tumor growth and suppresses the immune response in the tumor microenvironment.
  • A novel "lactate treatment plant" is developed to capture and convert lactate into reactive oxygen species (ROS) that have anti-tumor effects.
  • This system, using lactate oxidase and copper ions, significantly enhances lactate breakdown and promotes immune responses, achieving 88% tumor inhibition in model tests.

Article Abstract

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 (PLNP). 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 (HO), 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684183PMC
http://dx.doi.org/10.1186/s12951-021-01169-9DOI Listing

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