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<p>M1 macrophages (M1φ) are pivotal drivers in the progression from non-alcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Longitudinal monitoring of intrahepatic M1φ could facilitate non-invasive diagnosis of NASH, yet achieving specific and sensitive <i>in vivo</i> imaging of M1φ remains challenging due to the nonspecific phagocytic activity common to all phenotypic macrophages. In this study, we developed a dual-target-recognizing photoacoustic nanoprobe that can target glucose transporters (GLUTs) and be selectively activated by nitric oxide (NO). Benefiting from its enhanced affinity for M1φ and decent responsive capability to NO, the probe exhibited favorable imaging performance toward M1φ in <i>ex vivo</i> experiments. Following systemic administration in diabetic mice, the probe rapidly accumulated in the liver, where it was selectively internalized by M1φ via specific recognition between glucose molecules and GLUTs, further inducing a NO-triggered enhancement of the photoacoustic signal. Distinct photoacoustic signal enhancement patterns were observed between NAFL and NASH livers, enabling non-invasive <i>in vivo</i> discrimination of NASH. This study proposes a novel strategy using a dual-target-recognizing probe to improve the selectivity and sensitivity of <i>in vivo</i> M1φ imaging, while also providing new insights for the non-invasive diagnosis of NASH.</p>

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Visualizing hepatic M1 macrophages with a dual-target-recognizing photoacoustic nanoprobe for identifying non-alcoholic steatohepatitis

  • 期刊论文

  • 发表日期：

    2026年5月6日

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  • Meng Zhang,
  • Yiyue Wang,
  • Qihong Wu,
  • Ran Sun,
  • Lu Ye,
  • Lu Zhang,
  • Julin Wang,
  • Minrui Liu,
  • Hanrui Liu,
  • Haiming Fan,
  • Yingkun Guo

摘要

M1 macrophages (M1φ) are pivotal drivers in the progression from non-alcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Longitudinal monitoring of intrahepatic M1φ could facilitate non-invasive diagnosis of NASH, yet achieving specific and sensitive in vivo imaging of M1φ remains challenging due to the nonspecific phagocytic activity common to all phenotypic macrophages. In this study, we developed a dual-target-recognizing photoacoustic nanoprobe that can target glucose transporters (GLUTs) and be selectively activated by nitric oxide (NO). Benefiting from its enhanced affinity for M1φ and decent responsive capability to NO, the probe exhibited favorable imaging performance toward M1φ in ex vivo experiments. Following systemic administration in diabetic mice, the probe rapidly accumulated in the liver, where it was selectively internalized by M1φ via specific recognition between glucose molecules and GLUTs, further inducing a NO-triggered enhancement of the photoacoustic signal. Distinct photoacoustic signal enhancement patterns were observed between NAFL and NASH livers, enabling non-invasive in vivo discrimination of NASH. This study proposes a novel strategy using a dual-target-recognizing probe to improve the selectivity and sensitivity of in vivo M1φ imaging, while also providing new insights for the non-invasive diagnosis of NASH.