Tangbing Xu, Qiming Ma, Chi Zhang, Xiaoyan He, Qian Wang, Yunfeng Wu, Kunpeng Qin, Faxue Liao, Ping Zhou, Pengfei Xu, Jialai Yang, Junjun Yang, Jun Chang, Lei Qiao, Yong Hu
{"title":"一种用于骨肉瘤治疗的新型纳米药物：通过谷胱甘肽耗竭和抑制增强的协同PDT/PTT治疗引发铁吊。","authors":"Tangbing Xu, Qiming Ma, Chi Zhang, Xiaoyan He, Qian Wang, Yunfeng Wu, Kunpeng Qin, Faxue Liao, Ping Zhou, Pengfei Xu, Jialai Yang, Junjun Yang, Jun Chang, Lei Qiao, Yong Hu","doi":"10.1186/s12951-025-03380-4","DOIUrl":null,"url":null,"abstract":"<p><p>Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies. To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Interestingly, CSIR could harness the enhanced permeability and retention (EPR) effect to effectively enter tumors. Copper ions (Cu<sup>2+</sup>) within CSIR could react with the reductive intracellular environment, depleting glutathione (GSH) levels. Near-infrared (NIR) irradiation of CSIR further depleted GSH through reactive oxygen species (ROS) generation. Additionally, CSIR released sorafenib (SRF), which inhibited cystine-glutamate antiporter system xCT (xCT), thereby blocking GSH biosynthesis. RNA sequencing data confirmed ferroptosis induction by CSIR. This synergistic strategy of GSH depletion-induced ferroptosis, enhanced PDT, and photothermal cascade holds promise for improved osteosarcoma treatment and future nanomedicine design.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"323"},"PeriodicalIF":10.6000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039277/pdf/","citationCount":"0","resultStr":"{\"title\":\"A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy.\",\"authors\":\"Tangbing Xu, Qiming Ma, Chi Zhang, Xiaoyan He, Qian Wang, Yunfeng Wu, Kunpeng Qin, Faxue Liao, Ping Zhou, Pengfei Xu, Jialai Yang, Junjun Yang, Jun Chang, Lei Qiao, Yong Hu\",\"doi\":\"10.1186/s12951-025-03380-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies. To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Interestingly, CSIR could harness the enhanced permeability and retention (EPR) effect to effectively enter tumors. Copper ions (Cu<sup>2+</sup>) within CSIR could react with the reductive intracellular environment, depleting glutathione (GSH) levels. Near-infrared (NIR) irradiation of CSIR further depleted GSH through reactive oxygen species (ROS) generation. Additionally, CSIR released sorafenib (SRF), which inhibited cystine-glutamate antiporter system xCT (xCT), thereby blocking GSH biosynthesis. RNA sequencing data confirmed ferroptosis induction by CSIR. This synergistic strategy of GSH depletion-induced ferroptosis, enhanced PDT, and photothermal cascade holds promise for improved osteosarcoma treatment and future nanomedicine design.</p>\",\"PeriodicalId\":16383,\"journal\":{\"name\":\"Journal of Nanobiotechnology\",\"volume\":\"23 1\",\"pages\":\"323\"},\"PeriodicalIF\":10.6000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039277/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Nanobiotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1186/s12951-025-03380-4\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nanobiotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s12951-025-03380-4","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
A novel nanomedicine for osteosarcoma treatment: triggering ferroptosis through GSH depletion and inhibition for enhanced synergistic PDT/PTT therapy.
Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies. To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Interestingly, CSIR could harness the enhanced permeability and retention (EPR) effect to effectively enter tumors. Copper ions (Cu2+) within CSIR could react with the reductive intracellular environment, depleting glutathione (GSH) levels. Near-infrared (NIR) irradiation of CSIR further depleted GSH through reactive oxygen species (ROS) generation. Additionally, CSIR released sorafenib (SRF), which inhibited cystine-glutamate antiporter system xCT (xCT), thereby blocking GSH biosynthesis. RNA sequencing data confirmed ferroptosis induction by CSIR. This synergistic strategy of GSH depletion-induced ferroptosis, enhanced PDT, and photothermal cascade holds promise for improved osteosarcoma treatment and future nanomedicine design.
期刊介绍：
Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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