Design of MOFs-based spatially confined catalysis-driven intelligent responsive photoacoustic probe for deep-tissue
Wenfang Huang1, Rui Bai1, Mei Man2
1Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Guangxi Colleges and Universities Key Laboratory of Efficient Utilization of Special Resources in Southeast Guangxi, College of Chemistry and Food Science, Yulin Normal University, Yulin, 537000, China.
Abstract:
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.
