Responsive Organic MRI Probes for Functional Boundary Delineation: Tumor Microenvironment Response, Responsive Sites, and Responsive Mechanisms

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Abstract
Precise identification and quantitative analysis of the functional boundary are essential for accurate diagnosis and treatment. This not only relates to the precise delineation of lesion areas but also holds significant scientific importance for revealing tumor formation, progression, invasion, and metastasis across the functional boundary. The complex tumor microenvironment and variable biological characteristics present unprecedented opportunities and challenges for precise identification and quantification of the functional boundary. Unlike conventional magnetic resonance imaging (MRI) probes, responsive organic MRI probes rely on local tumor stimuli to trigger covalent bond cleavage, aggregation/disaggregation, conformational rearrangement, electronic state transitions, exchange rate changes, radical/nonradical interconversions, etc., ultimately translating into measurable MR readout signals. This provides a novel technical pathway for the precise determination and quantitative analysis of functional boundaries. In recent years, focusing on features such as pH decrease, protease overexpression, elevated levels of reactive oxygen species (ROS), and hypoxia, responsive organic MRI probes have gradually formed a relatively systematic research framework. This review follows a clear route from microenvironmental abnormality to responsive site, stimulus-triggered event, and MR readout, systematically reviewing the design principles and response mechanisms of responsive sites under different stimulus types. It points out that the key challenge facing current imaging probes is not the continuous addition of functions but establishing clearer, more quantifiable, and biologically interpretable imaging strategies, providing theoretical support and research ideas for achieving a precise determination and quantitative analysis of the functional boundary.
Funding Information
  • Natural Science Foundation of Zhejiang Province (ZCLQ24C1002)
  • Natural Science Foundation of Ningbo (2024QL026)
  • National Natural Science Foundation of China (32571585)
  • National Natural Science Foundation of China (52501220)

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