Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, 30602, USA.
Small. 2022 Apr;18(17):e2200710. doi: 10.1002/smll.202200710. Epub 2022 Mar 18.
Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation.
原位激活辐射以增强放射疗法疗效的治疗方法是非常需要的。在此，胆固醇的生物合成前体 7-脱氢胆固醇（7-DHC）被用作放射增敏剂，利用其引发自由基链式反应的能力进行研究。研究表明，7-DHC 可以与辐射诱导的活性氧反应，并反过来促进癌细胞中的脂质过氧化、双链断裂和线粒体损伤。为了实现有效的递送，将 7-DHC 封装到聚（乳酸-共-乙醇酸）纳米颗粒中，形成 7-DHC@PLGA NPs。在 CT26 荷瘤小鼠中进行测试时，7-DHC@PLGA NPs 显著增强了放射疗法的疗效，使 30%的治疗动物完全消除了肿瘤。治疗后，7-DHC 转化为胆固醇，不会引起可检测的副作用或高钙血症。7-DHC@PLGA NPs 是一种具有临床转化潜力的辐射响应性增敏剂。
