Near-Infrared Nano-Optogenetic Activation of Cancer Immunotherapy via Engineered Bacteria.

Adv Mater

National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan, 430074, P. R. China.

Published: February 2023

AI Article Synopsis

  • - The study explores the use of engineered E. coli Nissle 1917 (EcN) to improve cancer treatment by making it respond to blue light, thereby safely delivering a protein (flaB) that activates the immune system.
  • - The engineered EcN is paired with lanthanide upconversion nanoparticles (UCNPs) that emit blue light when exposed to near-infrared (NIR) light, triggering the release of flaB to stimulate an immune response through Toll-like receptor 5 on macrophages.
  • - This innovative approach leads to significant tumor shrinkage in various cancer models with minimal side effects, showcasing the potential of combining nanotechnology and bacterial therapies for effective cancer immunotherapy.

Article Abstract

Certain anaerobic microbes with the capability to colonize the tumor microenvironment tend to express the heterologous gene in a sustainable manner, which will inevitably compromise the therapeutic efficacy and induce off-tumor toxicity in vivo. To improve the therapeutic precision and controllability of bacteria-based therapeutics, Escherichia coli Nissle 1917 (EcN), engineered to sense blue light and release the encoded flagellin B (flaB), is conjugated with lanthanide upconversion nanoparticles (UCNPs) for near-infrared (NIR) nano-optogenetic cancer immunotherapy. Upon 808 nm photoirradiation, UCNPs emit at the blue region to photoactivate the EcN for secretion of flaB, which subsequently binds to Toll-like receptor 5 expressed on the membrane of macrophages for activating immune response via MyD88-dependent signal pathway. Such synergism leads to significant tumor regression in different tumor models and metastatic tumors with negligible side effects. These studies based on the NIR nano-optogenetic platform highlight the rational of leveraging the optogenetic tools combined with natural propensity of certain bacteria for cancer immunotherapy.

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Source
http://dx.doi.org/10.1002/adma.202207198DOI Listing

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