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

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Asian Journal of Pharmaceutical Sciences Pub Date : 2023-09-01 DOI:10.1016/j.ajps.2023.100850
Xiaomin Su , Boshu Ouyang , Yao Liu , Yang Wang , Ruizhe Xu , Lili Niu , NanNan Li , Ce Xu , Zanya Sun , Huishu Guo , Zhiqing Pang , Xiangrong Yu
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摘要

与正常细胞相比,肿瘤细胞维持快速增殖所需的高营养和能量为实施饥饿治疗提供了潜在的有利途径。然而,常规的饥饿治疗,如葡萄糖耗竭和血管血栓形成,会导致全身毒性并加剧肿瘤缺氧。在此,我们开发了一种新的“关闭阀门”饥饿策略,通过关闭葡萄糖转运蛋白1(GLUT1)的阀门来实现。具体而言,将双氢青蒿素(DHA)、2,20-偶氮双[2-(2-咪唑啉-2-基)丙烷]二盐酸盐(AI)和Ink共包封在藻酸钠(ALG)水凝胶中。在1064nm激光照射后,AI迅速分解为烷基自由基(R•),这通过产生活性氧加剧了DHA诱导的线粒体损伤,并进一步减少了三磷酸腺苷(ATP)的合成。同时,R•的产生通过抑制GLUT1促进了DHA诱导的饥饿治疗,GLUT1反过来又减少了葡萄糖摄取。系统的体内和体外结果表明,这种用于诱导肿瘤细胞饥饿的自由基增强的“瓣膜关闭”策略在降低葡萄糖摄取和ATP水平方面是有效的。这种综合策略通过有效的肿瘤抑制诱导肿瘤饥饿,为控制、精确和协同的肿瘤治疗开辟了一条新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered “valve-off” starvation therapy

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.

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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
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.
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