Biosynthesis of Cu2-xSe Nanocatalyst Within Probiotics for Repolarization of Tumor Associated Macrophages to Boost Mild Photothermal Sensitized Chemodynamic Immunotherapy

  • Adv Healthc Mater. 2026 Jan 4:e03745. doi: 10.1002/adhm.202503745.
Meichan Wu  1 ,  Puze Li  1  2 ,  Xin Xin  3 ,  Cheng Song  1 ,  Xiangliang Yang  1  4  5 ,  Qingxia Xu  2 ,  Yan Liu  6 ,  Yong Shen  2 ,  Guoping Wang  1  7 ,  Jun Hu  1  4  5
Affiliations
  • 1. National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 2. Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
  • 3. Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4. Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, China.
  • 5. Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 6. Department of Gastroenterology, Wuhan Eighth Hospital, Wuhan, China.
  • 7. Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
PMID: 41486808 DOI: 10.1002/adhm.202503745
Abstract

The activation and infiltration of cytotoxic T lymphocytes (CTLs) are the key of tumor immunotherapy. However, the suppressive tumor immune microenvironment usually inhibits the function of CTLs. Tumor-associated macrophages (TAMs) play an important role in remodeling the tumor immune microenvironment. In this work, probiotic Escherichia coli Nissle 1917 (EcN) is used as a bioreactor to achieve intracellular synthesis of copper selenide nanoparticles (Cu2-xSe NPs), giving Cu2-xSe@EcN, which effectively repolarize macrophages from pro-tumor M2 phenotype to anti-tumor M1 phenotype mainly through activating MAPK signaling pathway. The synthesized Cu2-xSe NPs exhibited excellent photothermal performance, inducing hyperthermia-sensitized Fenton-like reaction to catalyze the generation of hydroxyl radical from H2O2, then resulted in immunogenic death effect of tumor cells and the repolarization of M2 macrophages. Combined with surface-expressed pathogen-associated molecular patterns (PAMPs) of bacteria, Cu2-xSe@EcN synergistically promoted DCs maturation and TAMs reprogramming, eventually promoting the infiltration and activation of T cells. Therefore, the bacteria-inorganic hybrid nanomaterials showed satisfied effect in inhibiting tumor growth and recurrence.

Keywords
Cu2‐xSe nanocatalyst; chemodynamic immunotherapy; engineered probiotics; mild photothermal; tumor‐associated macrophage repolarization.
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