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Related Experiment Video

Updated: Jan 12, 2026

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Responsive Photosensitizer Precursors Reverse Drug-Induced Secondary Immunosuppression.

Shan Zuo1, Huiyi Liu1, Gangwei Jiang1

  • 1State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.

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|November 6, 2025
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This study developed a novel photosensitizer precursor (NP-YB-5) to reprogram tumor-associated macrophages (TAMs). This approach effectively treats primary and metastatic tumors by reversing drug-induced immunosuppression.

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Area of Science:

  • Immunology
  • Oncology
  • Photodynamic Therapy

Background:

  • Pharmacological cancer treatments can cause secondary immunosuppression, hindering efficacy.
  • Tumor-associated macrophages (TAMs) often exist in an immunosuppressive M2 phenotype.
  • Reprogramming TAMs to an M1 phenotype via photosensitization can reverse immunosuppression.

Purpose of the Study:

  • To develop a novel photosensitizer precursor (PP) with enhanced macrophage specificity and photosensitivity.
  • To overcome the limitations of current photosensitizers in addressing drug-induced secondary immunosuppression.
  • To evaluate the efficacy of the novel PP in reprogramming TAMs and treating tumors.

Main Methods:

  • A proximity-driven strategy was employed to optimize photosensitizer precursor (PP) activation within M2 macrophages.
  • Integrated screening identified a novel PP, NP-YB-5, with superior performance.
  • Phototherapy mediated by NP-YB-5 was used to treat primary and metastatic tumors in a preclinical model.

Main Results:

  • NP-YB-5 demonstrated superior efficacy (72.1%) in inducing macrophage polarization compared to controls.
  • Phototherapy with NP-YB-5 effectively eliminated primary tumors and inhibited distal tumor progression.
  • A statistical cure rate of 85% was achieved in the treated group.

Conclusions:

  • The developed proximity-driven strategy enhances PP activation efficiency and selectivity in M2 macrophages.
  • NP-YB-5 represents a potent molecular tool for macrophage-mediated photosensitization.
  • This approach offers a promising strategy for overcoming drug-induced secondary immunosuppression in cancer therapy.