Xiaomin Su , Boshu Ouyang , Yao Liu , Yang Wang , Ruizhe Xu , Lili Niu , NanNan Li , Ce Xu , Zanya Sun , Huishu Guo , Zhiqing Pang , Xiangrong Yu
{"title":"低温光热诱导的烷基自由基释放促进了双氢青蒿素触发的“关阀”饥饿治疗","authors":"Xiaomin Su , Boshu Ouyang , Yao Liu , Yang Wang , Ruizhe Xu , Lili Niu , NanNan Li , Ce Xu , Zanya Sun , Huishu Guo , Zhiqing Pang , Xiangrong Yu","doi":"10.1016/j.ajps.2023.100850","DOIUrl":null,"url":null,"abstract":"<div><p>The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R<sup>•</sup>), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R<sup>•</sup> facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic <em>in vivo</em> and <em>in vitro</em> results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100850"},"PeriodicalIF":10.7000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered “valve-off” starvation therapy\",\"authors\":\"Xiaomin Su , Boshu Ouyang , Yao Liu , Yang Wang , Ruizhe Xu , Lili Niu , NanNan Li , Ce Xu , Zanya Sun , Huishu Guo , Zhiqing Pang , Xiangrong Yu\",\"doi\":\"10.1016/j.ajps.2023.100850\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R<sup>•</sup>), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R<sup>•</sup> facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic <em>in vivo</em> and <em>in vitro</em> results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.</p></div>\",\"PeriodicalId\":8539,\"journal\":{\"name\":\"Asian Journal of Pharmaceutical Sciences\",\"volume\":\"18 5\",\"pages\":\"Article 100850\"},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asian Journal of Pharmaceutical Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1818087623000776\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1818087623000776","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.
期刊介绍:
The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.