Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis
Radiotherapy (RT) incorporated multidisciplinary treatment is producing excellent clinical results, but its efficacy in treating late-stage gastric cancer is constrained by radioresistance and RT-related toxicity. Especially, since reactive oxygen species are the pivotal effectual molecules of ioniz...
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1171450/full |
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| author | Hongwei Wang Hongwei Wang Hongyan Niu Xi Luo Nan Zhu Jingfeng Xiang Yan He Zhian Chen Guoxin Li Yanfeng Hu |
| author_facet | Hongwei Wang Hongwei Wang Hongyan Niu Xi Luo Nan Zhu Jingfeng Xiang Yan He Zhian Chen Guoxin Li Yanfeng Hu |
| author_sort | Hongwei Wang |
| collection | DOAJ |
| description | Radiotherapy (RT) incorporated multidisciplinary treatment is producing excellent clinical results, but its efficacy in treating late-stage gastric cancer is constrained by radioresistance and RT-related toxicity. Especially, since reactive oxygen species are the pivotal effectual molecules of ionizing radiation, improving ROS production by nanoparticles and other pharmacological modulation to amplify oxidation of polyunsaturated fatty acids and subsequent ferroptotic cell death is shown to enhance cancer cell radioresponse. Herein, we constructed a nanosystem by loading Pyrogallol (PG), a polyphenol compound and ROS generator, into mesoporous organosilica nanoparticles named as MON@pG. The nanoparticles exhibit proper size distribution with amplified ROS production and substantial glutathione depletion under X-ray radiation in gastric cancer cell line. Meanwhile, MON@PG enhanced radiosensitivity of gastric cancer in xenograft tumor model by ROS-mediated accumulation of DNA damage and apoptosis. Furthermore, this augmented oxidative process induced mitochondrial dysfunction and ferroptosis. In summary, MON@PG nanoparticles show the capacity to improve RT potency in gastric cancer by disrupting redox balance and augmenting ferroptosis. |
| format | Article |
| id | doaj-art-08893357b7ac4d359dc4da2e7f966a26 |
| institution | OA Journals |
| issn | 2296-4185 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-08893357b7ac4d359dc4da2e7f966a262025-08-20T02:09:11ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-04-011110.3389/fbioe.2023.11714501171450Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosisHongwei Wang0Hongwei Wang1Hongyan Niu2Xi Luo3Nan Zhu4Jingfeng Xiang5Yan He6Zhian Chen7Guoxin Li8Yanfeng Hu9Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Longgang Central Hospital of Shenzhen, Shenzhen, ChinaDepartment of Clinical Laboratory, The Affiliated Huai’an Hospital of Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pathology, Longgang Central Hospital of Shenzhen, Shenzhen, ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaRadiotherapy (RT) incorporated multidisciplinary treatment is producing excellent clinical results, but its efficacy in treating late-stage gastric cancer is constrained by radioresistance and RT-related toxicity. Especially, since reactive oxygen species are the pivotal effectual molecules of ionizing radiation, improving ROS production by nanoparticles and other pharmacological modulation to amplify oxidation of polyunsaturated fatty acids and subsequent ferroptotic cell death is shown to enhance cancer cell radioresponse. Herein, we constructed a nanosystem by loading Pyrogallol (PG), a polyphenol compound and ROS generator, into mesoporous organosilica nanoparticles named as MON@pG. The nanoparticles exhibit proper size distribution with amplified ROS production and substantial glutathione depletion under X-ray radiation in gastric cancer cell line. Meanwhile, MON@PG enhanced radiosensitivity of gastric cancer in xenograft tumor model by ROS-mediated accumulation of DNA damage and apoptosis. Furthermore, this augmented oxidative process induced mitochondrial dysfunction and ferroptosis. In summary, MON@PG nanoparticles show the capacity to improve RT potency in gastric cancer by disrupting redox balance and augmenting ferroptosis.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1171450/fullgastric cancerradiosensitivityROS generationGSH depletionferroptosis |
| spellingShingle | Hongwei Wang Hongwei Wang Hongyan Niu Xi Luo Nan Zhu Jingfeng Xiang Yan He Zhian Chen Guoxin Li Yanfeng Hu Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis Frontiers in Bioengineering and Biotechnology gastric cancer radiosensitivity ROS generation GSH depletion ferroptosis |
| title | Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis |
| title_full | Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis |
| title_fullStr | Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis |
| title_full_unstemmed | Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis |
| title_short | Radiosensitizing effects of pyrogallol-loaded mesoporous or-ganosilica nanoparticles on gastric cancer by amplified ferroptosis |
| title_sort | radiosensitizing effects of pyrogallol loaded mesoporous or ganosilica nanoparticles on gastric cancer by amplified ferroptosis |
| topic | gastric cancer radiosensitivity ROS generation GSH depletion ferroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1171450/full |
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