Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy
Lysosomes is emerging as a promising therapeutic target for improving immunotherapy, which dysfunction would trigger lysosomal membrane permeabilization increase and subsequent leakage of reduced iron, which contributed to ferroptosis through cell-intrinsic Fenton chemistry. However, the integrity o...
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Elsevier
2025-04-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425001103 |
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| author | Zhian Chen Yutong Wang Zhenhao Li Meijuan Chen Yingshi Li Chuyue Lu Zhenyu Lin Hua Zheng Lujia Chen Qianbing Zhang |
| author_facet | Zhian Chen Yutong Wang Zhenhao Li Meijuan Chen Yingshi Li Chuyue Lu Zhenyu Lin Hua Zheng Lujia Chen Qianbing Zhang |
| author_sort | Zhian Chen |
| collection | DOAJ |
| description | Lysosomes is emerging as a promising therapeutic target for improving immunotherapy, which dysfunction would trigger lysosomal membrane permeabilization increase and subsequent leakage of reduced iron, which contributed to ferroptosis through cell-intrinsic Fenton chemistry. However, the integrity of lysosomal membranes is not susceptible to disrupt, owing to the presence of several Endo-lysosomal damage-response mechanisms. Herein, we developed a lysosome-targeted photosensitizer (TLA), which possessed robust light stability, good bio-compatibility, and high photodynamic therapy (PDT) effect. Upon internalized by cancer cells, TLA was specifically accumulated in lysosome, and which would destroy the integrity of lysosomal membranes and inhibit protective autophagy upon exposure to light irradiation. Subsequently, the cancer cells were suffered from ferroptosis through triggering cell-intrinsic Fenton chemistry and mitochondrial dysfunction, which would release damage-associated molecular pattern molecules (DAMPs) to induce immunogenic cell death and remodel immunosuppressive tumor microenvironment. Notably, combined with PD-L1 antibody and TLA could greatly potentiate the immune response and exhibit highest anti-tumor effects. In summary, this novel lysosome-targeted photosensitizer could serve as a promising strategy for the treatment of colorectal cancer. |
| format | Article |
| id | doaj-art-5689d3f175e44c5ba4db8c17afa752ad |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-5689d3f175e44c5ba4db8c17afa752ad2025-02-11T04:35:23ZengElsevierMaterials Today Bio2590-00642025-04-0131101552Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapyZhian Chen0Yutong Wang1Zhenhao Li2Meijuan Chen3Yingshi Li4Chuyue Lu5Zhenyu Lin6Hua Zheng7Lujia Chen8Qianbing Zhang9Zhongshan City People's Hospital, Zhongshan, 528403, ChinaThe First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, ChinaThe First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, ChinaState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaCancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaCancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Corresponding author.Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China; Corresponding author.Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China; Corresponding author.Lysosomes is emerging as a promising therapeutic target for improving immunotherapy, which dysfunction would trigger lysosomal membrane permeabilization increase and subsequent leakage of reduced iron, which contributed to ferroptosis through cell-intrinsic Fenton chemistry. However, the integrity of lysosomal membranes is not susceptible to disrupt, owing to the presence of several Endo-lysosomal damage-response mechanisms. Herein, we developed a lysosome-targeted photosensitizer (TLA), which possessed robust light stability, good bio-compatibility, and high photodynamic therapy (PDT) effect. Upon internalized by cancer cells, TLA was specifically accumulated in lysosome, and which would destroy the integrity of lysosomal membranes and inhibit protective autophagy upon exposure to light irradiation. Subsequently, the cancer cells were suffered from ferroptosis through triggering cell-intrinsic Fenton chemistry and mitochondrial dysfunction, which would release damage-associated molecular pattern molecules (DAMPs) to induce immunogenic cell death and remodel immunosuppressive tumor microenvironment. Notably, combined with PD-L1 antibody and TLA could greatly potentiate the immune response and exhibit highest anti-tumor effects. In summary, this novel lysosome-targeted photosensitizer could serve as a promising strategy for the treatment of colorectal cancer.http://www.sciencedirect.com/science/article/pii/S2590006425001103Photodynamic therapyLysosomal targetingFerroptosisAutophagy inhibitionImmunogenic cell death |
| spellingShingle | Zhian Chen Yutong Wang Zhenhao Li Meijuan Chen Yingshi Li Chuyue Lu Zhenyu Lin Hua Zheng Lujia Chen Qianbing Zhang Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy Materials Today Bio Photodynamic therapy Lysosomal targeting Ferroptosis Autophagy inhibition Immunogenic cell death |
| title | Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy |
| title_full | Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy |
| title_fullStr | Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy |
| title_full_unstemmed | Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy |
| title_short | Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy |
| title_sort | improving ferroptosis mediated immunotherapy for colorectal cancer through lysosome targeted photodynamic therapy |
| topic | Photodynamic therapy Lysosomal targeting Ferroptosis Autophagy inhibition Immunogenic cell death |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425001103 |
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