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Updated: Jun 7, 2025
12:58
Characterizing Individual Protein Aggregates by Infrared Nanospectroscopy and Atomic Force Microscopy
Published on: September 12, 2019
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Enzymatically catalyzed molecular aggregation
Wen-Jin Wang1,2,3, Rongyuan Zhang1,2, Liping Zhang1,2
1Clinical Translational Research Center of Aggregation-Induced Emission, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen, Guangdong, 518172, China.
Nature Communications
|November 18, 2024
Summary
Scientists developed a novel cancer therapy using a tumor-targeting photosensitizer (AIE-PS) activated by an enzyme (GGT). This approach enhances drug aggregation, leading to effective cancer cell death and demonstrating significant anti-cancer effects in vivo.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Molecular Imaging
Background:
- Controlling small molecule aggregation in vivo is challenging due to complex biological environments.
- Tumor-specific enzyme activity offers a potential target for localized drug activation.
- Aggregation-induced emission photosensitizers (AIE-PS) show promise for photodynamic therapy (PDT).
Purpose of the Study:
- To achieve tumor-targeted aggregation of an AIE-PS, TBmA, using enzyme catalysis.
- To investigate the mechanism of enzyme-activated aggregation and its therapeutic effects.
- To evaluate the in vivo anti-cancer efficacy of the developed system.
Main Methods:
- Synthesis of a GGT-activatable AIE-PS, TBmA-Glu.
- In vitro studies on enzyme-catalyzed activation, aggregation, and cancer cell death induction (ferroptosis).
- In vivo evaluation in mouse models (xenograft and orthotopic liver cancer).
Main Results:
- GGT successfully cleaved TBmA-Glu, releasing TBmA and inducing aggregation-enhanced emission and photodynamic activity.
- TBmA-Glu treatment led to glutathione depletion, lipid peroxidation, and ferroptosis in cancer cells.
- Significant tumor inhibition was observed in both xenograft and orthotopic liver cancer models.
Conclusions:
- Enzymatic activation of AIE-PS is an effective strategy for intracellular small molecule aggregation control.
- GGT-targeted AIE-PS demonstrates potent anti-cancer effects via photodynamic therapy and ferroptosis induction.
- This approach offers a promising platform for developing innovative therapeutic strategies for various diseases.
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