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Microenvironment-Triggered Signal Amplification for Dual-Modal Fluorescence/MRI of Hepatocellular Carcinoma
Jihong Liu1, Shiyun Xu1, Ting Yang1
1Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Shanghai Key Laboratory of Functional Materials Chemistry, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.
A novel nanoprobe enhances dual-modal fluorescence/magnetic resonance imaging (FL/MRI) for hepatocellular carcinoma (HCC) detection. It becomes signal-active in acidic tumor environments, improving imaging sensitivity and resolution for better tumor diagnosis.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Oncology
Background:
- Dual-modal fluorescence/magnetic resonance imaging (FL/MRI) shows promise for hepatocellular carcinoma (HCC) detection.
- Current FL/MRI methods face limitations due to weak signal synergy and poor tumor microenvironment responsiveness.
Purpose of the Study:
- To develop a tumor-microenvironment-responsive nanoprobe for enhanced FL/MRI of HCC.
- To achieve signal-silent operation initially, with triggered signal amplification in acidic tumor conditions.
Main Methods:
- Synthesized TCM-Gd-P NPs with amphiphilic polymer encapsulation for aggregation-induced emission luminogen (TCM-4COOLi) and Gd3+ ions.
- Investigated pH-triggered fluorescence enhancement and relaxivity changes.
- Evaluated *in vivo* performance in orthotopic HCC mice using FL/MRI.
Main Results:
- TCM-Gd-P NPs exhibited up to 12.4-fold fluorescence enhancement and an ~8.0-fold increase in longitudinal relaxivity under acidic conditions.
- *In vivo* studies showed 4.2-fold fluorescence and 3.3-fold MRI contrast enhancement in tumors.
- FL imaging provided molecular-level tumor margin delineation, while MRI offered high-resolution anatomical mapping.
Conclusions:
- Established a microenvironment-triggered, orthogonal signal amplification strategy for FL/MRI.
- Demonstrated a generalizable framework for intelligent solid-tumor diagnostics.
- Highlighted the complementary strengths of fluorescence and MRI for comprehensive HCC assessment.

