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Real-Time In Vivo Visualization of Tumor-Associated Macrophage Reprogramming Using a Nitric Oxide-Activatable NIR-II

Qian Chen1,2, Meng Li1, Tuanwei Li1

  • 1CAS Key Laboratory of Nano-Bio Interface, Suzhou Key Laboratory of Functional Molecular Imaging Technology, Division of Nanobiomedicine and i-Lab, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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Summary
This summary is machine-generated.

Researchers developed a novel nanoinducer to reprogram tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state. This strategy enhances anti-tumor immunity and allows for in vivo monitoring of macrophage repolarization.

Keywords:
NIR‐II windowratiometric imagingtumor microenvironmenttumor‐associated macrophage reprogramming

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Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Immunology

Background:

  • Tumor-associated macrophages (TAMs) are crucial in the tumor microenvironment (TME), often exhibiting an M2-like phenotype that fuels tumor progression.
  • Reprogramming TAMs to an anti-tumor phenotype, specifically M1-like, is a key therapeutic goal.

Purpose of the Study:

  • To develop and evaluate a nitric oxide (NO)-activatable near-infrared-II (NIR-II) nanoinducer (I/E@M2pep) for selective M2-like TAM targeting and repolarization.
  • To enable in vivo visualization of TAM repolarization using NIR-II fluorescence/photoacoustic imaging.

Main Methods:

  • Design of I/E@M2pep incorporating M2pep for targeting, IPI549 for M1 repolarization and NO production, and an NO-activatable NIR-II probe (ETNO).
  • Intravenous administration of I/E@M2pep in a mouse breast cancer model.
  • Assessment of M2-to-M1 repolarization via ratiometric NIR-II photoacoustic signals.
  • Combination therapy with a CD47 monoclonal antibody.

Main Results:

  • I/E@M2pep successfully targeted M2-like TAMs and induced M2-to-M1 repolarization, evidenced by NIR-II photoacoustic signal changes.
  • The nanoinducer facilitated simultaneous visualization and reprogramming of TAMs in vivo.
  • Combination therapy with anti-CD47 significantly boosted anti-tumor immunity and TME remodeling.

Conclusions:

  • The developed nanoinducer offers a dual function of facilitating and visualizing TAM repolarization in vivo.
  • This approach holds significant promise for advancing cancer therapy by modulating the TME and enhancing anti-tumor immunity.
  • The strategy could be broadly applied to study tumor initiation, metastasis, and treatment responses.