<p> An activatable photoacoustic probe based on metal-organic frameworks (MOFs) (denoted as MOFs@HRP&amp;ABTS) was designed for highly sensitive detection and precise imaging of H<sub>2</sub>O<sub>2</sub> in tumor microenvironment. The probe utilizes ZIF-8 as a pH-responsive carrier that undergoes selective degradation under acidic tumor conditions, enabling the controlled release of encapsulated horseradish peroxidase (HRP) and its substrate ABTS with tumor-specific precision. Upon release, HRP catalyzes the H<sub>2</sub>O<sub>2</sub>-dependent oxidation of ABTS to generate ABTS·⁺, a near-infrared-absorbing radical that elicits a significantly enhanced photoacoustic response. The system demonstrates a detection limit as low as 2.5 µM. Comprehensive experimental assessments confirm the probe’s high selectivity toward H<sub>2</sub>O<sub>2</sub> and excellent biocompatibility. In vivo studies using MCF-7 tumor-bearing mouse models enabled high-contrast, noninvasive visualization of tumor regions via photoacoustic imaging. By integrating the confined catalytic environment provided by the MOFs architecture with effective enzymatic stabilization, this work establishes a ternary “carrier-enzyme-substrate” cooperative system that surmounts the limited tissue penetration depth inherent in conventional optical probes. The resulting nanoplatform combines deep-tissue penetration, ultrahigh sensitivity, and noninvasive readout capabilities, offering a promising strategy for the precise detection of tumor biomarkers.</p> Graphical abstract <p></p>

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Design of MOFs-based spatially confined catalysis-driven intelligent responsive photoacoustic probe for deep-tissue H2O2 imaging in tumor microenvironment

  • Wenfang Huang,
  • Rui Bai,
  • Mei Man,
  • Shulong Wang,
  • Rong Wang,
  • Ling Liang,
  • Zhihui Luo,
  • Jiayao Xu

摘要

An activatable photoacoustic probe based on metal-organic frameworks (MOFs) (denoted as MOFs@HRP&ABTS) was designed for highly sensitive detection and precise imaging of H2O2 in tumor microenvironment. The probe utilizes ZIF-8 as a pH-responsive carrier that undergoes selective degradation under acidic tumor conditions, enabling the controlled release of encapsulated horseradish peroxidase (HRP) and its substrate ABTS with tumor-specific precision. Upon release, HRP catalyzes the H2O2-dependent oxidation of ABTS to generate ABTS·⁺, a near-infrared-absorbing radical that elicits a significantly enhanced photoacoustic response. The system demonstrates a detection limit as low as 2.5 µM. Comprehensive experimental assessments confirm the probe’s high selectivity toward H2O2 and excellent biocompatibility. In vivo studies using MCF-7 tumor-bearing mouse models enabled high-contrast, noninvasive visualization of tumor regions via photoacoustic imaging. By integrating the confined catalytic environment provided by the MOFs architecture with effective enzymatic stabilization, this work establishes a ternary “carrier-enzyme-substrate” cooperative system that surmounts the limited tissue penetration depth inherent in conventional optical probes. The resulting nanoplatform combines deep-tissue penetration, ultrahigh sensitivity, and noninvasive readout capabilities, offering a promising strategy for the precise detection of tumor biomarkers.

Graphical abstract