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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.

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|November 18, 2024
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Summary
This summary is machine-generated.

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.

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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.