A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy
“Glutamine addiction” is a unique feature of triple negative breast cancer (TNBC), which has a higher demand for glutamine and is more susceptible to glutamine depletion. Glutamine can be hydrolyzed to glutamate by glutaminase (GLS) for synthesis of glutathione (GSH), which is an important downstrea...
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| Format: | Article |
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Elsevier
2023-04-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423000376 |
| _version_ | 1797854312335933440 |
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| author | Cancan Yu Ningning Wang Xiangwu Chen Yue Jiang Yuxia Luan Wen Qin Wenxiu He |
| author_facet | Cancan Yu Ningning Wang Xiangwu Chen Yue Jiang Yuxia Luan Wen Qin Wenxiu He |
| author_sort | Cancan Yu |
| collection | DOAJ |
| description | “Glutamine addiction” is a unique feature of triple negative breast cancer (TNBC), which has a higher demand for glutamine and is more susceptible to glutamine depletion. Glutamine can be hydrolyzed to glutamate by glutaminase (GLS) for synthesis of glutathione (GSH), which is an important downstream of glutamine metabolic pathways in accelerating TNBC proliferation. Consequently, glutamine metabolic intervention suggests potential therapeutic effects against TNBC. However, the effects of GLS inhibitors are hindered by glutamine resistance and their own instability and insolubility. Therefore, it is of great interest to harmonize glutamine metabolic intervention for an amplified TNBC therapy. Unfortunately, such nanoplatform has not been realized. Herein, we reported a self-assembly nanoplatform (BCH NPs) with a core of the GLS inhibitor Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and photosensitizer Chlorin e6 (Ce6) and a shell of human serum albumin (HSA), enabling effective harmonization of glutamine metabolic intervention for TNBC therapy. BPTES inhibited the activity of GLS to block the glutamine metabolic pathways, thereby inhibiting the production of GSH to amplify the photodynamic effect of Ce6. While Ce6 not only directly killed tumor cells by producing excessive reactive oxygen species (ROS), but also deplete GSH to destroy redox balance, thus enhancing the effects of BPTES when glutamine resistance occurred. BCH NPs effectively eradicated TNBC tumor and suppressed tumor metastasis with favorable biocompatibility. Our work provides a new insight for photodynamic-mediated glutamine metabolic intervention against TNBC. |
| first_indexed | 2024-04-09T20:03:56Z |
| format | Article |
| id | doaj.art-158e8323647a481c9c8c056f82252666 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-09T20:03:56Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-158e8323647a481c9c8c056f822526662023-04-02T06:14:49ZengElsevierMaterials Today Bio2590-00642023-04-0119100577A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapyCancan Yu0Ningning Wang1Xiangwu Chen2Yue Jiang3Yuxia Luan4Wen Qin5Wenxiu He6Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, ChinaShandong University Hospital, Cheeloo College of Medicine, Shandong, University, Jinan 250012, China; Corresponding author. Wen QinKey Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China; Corresponding author. Wenxiu He School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.“Glutamine addiction” is a unique feature of triple negative breast cancer (TNBC), which has a higher demand for glutamine and is more susceptible to glutamine depletion. Glutamine can be hydrolyzed to glutamate by glutaminase (GLS) for synthesis of glutathione (GSH), which is an important downstream of glutamine metabolic pathways in accelerating TNBC proliferation. Consequently, glutamine metabolic intervention suggests potential therapeutic effects against TNBC. However, the effects of GLS inhibitors are hindered by glutamine resistance and their own instability and insolubility. Therefore, it is of great interest to harmonize glutamine metabolic intervention for an amplified TNBC therapy. Unfortunately, such nanoplatform has not been realized. Herein, we reported a self-assembly nanoplatform (BCH NPs) with a core of the GLS inhibitor Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and photosensitizer Chlorin e6 (Ce6) and a shell of human serum albumin (HSA), enabling effective harmonization of glutamine metabolic intervention for TNBC therapy. BPTES inhibited the activity of GLS to block the glutamine metabolic pathways, thereby inhibiting the production of GSH to amplify the photodynamic effect of Ce6. While Ce6 not only directly killed tumor cells by producing excessive reactive oxygen species (ROS), but also deplete GSH to destroy redox balance, thus enhancing the effects of BPTES when glutamine resistance occurred. BCH NPs effectively eradicated TNBC tumor and suppressed tumor metastasis with favorable biocompatibility. Our work provides a new insight for photodynamic-mediated glutamine metabolic intervention against TNBC.http://www.sciencedirect.com/science/article/pii/S2590006423000376Photodynamic therapyGlutamine metabolic interventionBPTESCe6Triple negative breast cancer |
| spellingShingle | Cancan Yu Ningning Wang Xiangwu Chen Yue Jiang Yuxia Luan Wen Qin Wenxiu He A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy Materials Today Bio Photodynamic therapy Glutamine metabolic intervention BPTES Ce6 Triple negative breast cancer |
| title | A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy |
| title_full | A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy |
| title_fullStr | A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy |
| title_full_unstemmed | A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy |
| title_short | A photodynamic-mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy |
| title_sort | photodynamic mediated glutamine metabolic intervention nanodrug for triple negative breast cancer therapy |
| topic | Photodynamic therapy Glutamine metabolic intervention BPTES Ce6 Triple negative breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423000376 |
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