An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance
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 desirabl...
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Elsevier
2025-04-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259000642500122X |
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| author | Hang Zou Pingping Wang Zhihao Bai Liping Liu Jingtong Wang Yanfang Cheng Bairong He Zujin Zhao Lei Zheng |
| author_facet | Hang Zou Pingping Wang Zhihao Bai Liping Liu Jingtong Wang Yanfang Cheng Bairong He Zujin Zhao Lei Zheng |
| author_sort | Hang Zou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-15eb332d5eee4590a1f8c6e298d91550 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-15eb332d5eee4590a1f8c6e298d915502025-02-12T05:31:42ZengElsevierMaterials Today Bio2590-00642025-04-0131101564An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistanceHang Zou0Pingping Wang1Zhihao Bai2Liping Liu3Jingtong Wang4Yanfang Cheng5Bairong He6Zujin Zhao7Lei Zheng8Department 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; De Feng Academy, Southern Medical University, Guangzhou, 510515, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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; De Feng Academy, Southern Medical University, Guangzhou, 510515, China; Department of Medical Laboratory, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, 341000, China; Corresponding author. Department 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.State Key Laboratory of Luminescent Materials and Devices, Key Laboratory of Luminescence from Molecular Aggregates of Guangdong Province, South China University of Technology, Guangzhou, 510515, China; Corresponding author. State Key Laboratory of Luminescent Materials and Devices, Key Laboratory of Luminescence from Molecular Aggregates of Guangdong Province, South China University of Technology, Guangzhou, 510640, China.Department 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; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S259000642500122XAggregation-induced emissionTherapeutic resistancePhotodynamic therapyTherapeutic sensitizerLysosomal membrane permeabilization |
| spellingShingle | Hang Zou Pingping Wang Zhihao Bai Liping Liu Jingtong Wang Yanfang Cheng Bairong He Zujin Zhao Lei Zheng An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance Materials Today Bio Aggregation-induced emission Therapeutic resistance Photodynamic therapy Therapeutic sensitizer Lysosomal membrane permeabilization |
| title | An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance |
| title_full | An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance |
| title_fullStr | An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance |
| title_full_unstemmed | An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance |
| title_short | An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance |
| title_sort | aggregation induced emission active lysosome hijacker sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance |
| topic | Aggregation-induced emission Therapeutic resistance Photodynamic therapy Therapeutic sensitizer Lysosomal membrane permeabilization |
| url | http://www.sciencedirect.com/science/article/pii/S259000642500122X |
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