Academic Journal
Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy
| Title: | Improving ferroptosis-mediated immunotherapy for colorectal cancer through lysosome-targeted photodynamic therapy |
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| Authors: | Zhian Chen, Yutong Wang, Zhenhao Li, Meijuan Chen, Yingshi Li, Chuyue Lu, Zhenyu Lin, Hua Zheng, Lujia Chen, Qianbing Zhang |
| Source: | Materials Today Bio, Vol 31, Iss , Pp 101552- (2025) |
| Publisher Information: | Elsevier, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine (General) LCC:Biology (General) |
| Subject Terms: | Photodynamic therapy, Lysosomal targeting, Ferroptosis, Autophagy inhibition, Immunogenic cell death, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2590-0064 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2590006425001103; https://doaj.org/toc/2590-0064 |
| DOI: | 10.1016/j.mtbio.2025.101552 |
| Access URL: | https://doaj.org/article/5689d3f175e44c5ba4db8c17afa752ad |
| Accession Number: | edsdoj.5689d3f175e44c5ba4db8c17afa752ad |
| Database: | Directory of Open Access Journals |
| ISSN: | 25900064 |
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| DOI: | 10.1016/j.mtbio.2025.101552 |
| Published in: | Materials Today Bio |
| Language: | English |