Related Experiment Video
Updated: May 24, 2025
A Photodynamic Approach to Study Function of Intracellular Vesicle Rupture
Published on: March 17, 2023
An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy
Hang Zou1,2, Pingping Wang1, Zhihao Bai1
1Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single-cell and Extracellular Vesicles, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Abstract:
Therapeutic resistance is a major challenge in clinical cancer theranostics, often leading to treatment failure and increased patient mortality. Breaking this therapeutic deadlock, enhancing the efficacy of clinical treatments, and ultimately improving patient survival rates are both highly desirable and significantly challenging goals. Herein, we have developed a new fluorescent luminogen, QM-DMAC, which features aggregation-induced emission (AIE), and exceptional viscosity-responsive properties. The AIE-active QM-DMAC can specifically stain lysosomes in tumor cells, offering a high signal-to-noise ratio and enabling specific visualization of variations in lysosomal viscosity, such as those induced by inflammation or autophagy. Furthermore, QM-DMAC effectively generates reactive oxygen species (ROS) under white light irradiation, which precisely induces ROS-mediated lysosomal membrane permeabilization (LMP) and lysosome rupture. This ultimately causes severe cell damage and restores the sensitivity of tumor cells to radiotherapy and chemotherapy. Thus, QM-DMAC serves as a highly efficient lysosome-targeting photosensitizer and an excellent therapeutic sensitizer. This innovative "lysosome hijacking" strategy significantly maximizes the efficacy of photodynamic therapy, conquering therapeutic resistance and boosting the synergistic therapeutic effect when integrated with conventional radiotherapy or chemotherapy. It provides a novel approach to the design of theranostic agents for clinical cancer theranostics.
Insights
This study introduces QM-DMAC, a novel fluorescent agent that targets cancer cell lysosomes. It overcomes therapeutic resistance by generating reactive oxygen species, enhancing chemotherapy and radiotherapy efficacy.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Therapeutic resistance is a critical barrier in cancer treatment, leading to poor patient outcomes.
- Developing novel agents to overcome drug resistance and enhance treatment efficacy is essential for improving cancer care.
Purpose of the Study:
- To develop a novel aggregation-induced emission (AIE) luminogen, QM-DMAC, for cancer theranostics.
- To investigate QM-DMAC's ability to target lysosomes, monitor viscosity changes, and act as a photosensitizer to overcome therapeutic resistance.
Main Methods:
- Synthesis and characterization of the AIE luminogen QM-DMAC.
- In vitro evaluation of QM-DMAC for lysosome targeting and viscosity sensing in tumor cells.
- Assessment of QM-DMAC-mediated reactive oxygen species (ROS) generation and its effect on lysosomal membrane permeabilization (LMP).
- Evaluation of QM-DMAC's efficacy in restoring sensitivity to radiotherapy and chemotherapy in resistant cancer cells.
Main Results:
- QM-DMAC exhibits AIE properties and specifically stains tumor cell lysosomes with high signal-to-noise ratio.
- QM-DMAC effectively visualizes lysosomal viscosity variations linked to cellular states like inflammation and autophagy.
- White light irradiation of QM-DMAC induces ROS generation, leading to LMP and lysosome rupture.
- QM-DMAC treatment resensitizes resistant cancer cells to conventional radiotherapy and chemotherapy, demonstrating its potential as a therapeutic sensitizer.
Conclusions:
- QM-DMAC is a novel lysosome-targeting AIE luminogen with viscosity-responsive and photosensitizing capabilities.
- The "lysosome hijacking" strategy using QM-DMAC effectively enhances photodynamic therapy and overcomes therapeutic resistance.
- QM-DMAC shows promise as a theranostic agent for improving synergistic effects with conventional cancer treatments.
More Related Videos
11:04An In-House-Built and Light-Emitting-Diode-Based Photodynamic Therapy Device for Enhancing Verteporfin Cytotoxicity in a 2D Cell Culture Model
Published on: January 13, 2023
08:03Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
