7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy.
7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy.
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7-脱氢胆固醇包封的聚合物纳米颗粒作为增强放射治疗的辐射敏感剂。
DOI：
10.1002/smll.202200710
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发表时间：
2022-04
期刊：
影响因子：
13.3
通讯作者：
Xie, Jin
中科院分区：
文献类型：
--
作者：
Delahunty, Ian;Li, Jianwen;Jiang, Wen;Lee, Chaebin;Yang, Xueyuan;Kumar, Anil;Liu, Zhi;Zhang, Weizhong;Xie, Jin
非常需要可以通过原位辐射激活以增强放射治疗功效的治疗剂。在此，我们探索7-脱氢胆固醇（7-DHC），胆固醇的生物合成前体，作为放射增敏剂，利用其传播自由基链反应的能力。我们的研究表明，7-DHC可以与辐射诱导的活性氧反应，进而促进癌细胞中的脂质过氧化、双链断裂和线粒体损伤。为了有效递送，7-DHC被封装到聚（乳酸-共-乙醇酸）纳米颗粒中，形成7-DHC@PLGA纳米颗粒。当在CT 26荷瘤小鼠中测试时，7-DHC@PLGA NP显著增强了放射治疗的功效，在30%的治疗动物中导致完全肿瘤根除。治疗后，7-DHC转化为胆固醇，不会引起可检测到的副作用或高钙血症。7-DHC@PLGA NP代表了在临床转化中具有巨大潜力的辐射响应性敏化剂。7-载脱氢胆固醇（7-DHC）的PLGA纳米粒是一种很有前途的放射增敏剂。7-DHC与辐射诱导的自由基反应，进而在多不饱和脂肪酸之间传播自由基链式反应。这导致脂质过氧化和线粒体损伤，增强放射治疗的疗效。治疗后，7-DHC代谢为胆固醇，对宿主的副作用最小。
Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, we explore 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate free radical chain reaction. Our 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. 7-Dehydrocholesterol (7-DHC)-loaded PLGA nanoparticles are a promising radiosensitizer. 7-DHC reacts with radiation-induced radicals, in turn propagating radical chain reactions among polyunsaturated fatty acids. This leads to lipid peroxidation and mitochondrial damage, enhancing the efficacy of radiation therapy. After treatment, 7-DHC is metabolized to cholesterol, causing minimum side effects to the host.
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影响因子：
6.2
作者：
Delaney, G;Jacob, S;Barton, M
通讯作者：
Barton, M
影响因子：
3.4
作者：
Lamberson CR;Muchalski H;McDuffee KB;Tallman KA;Xu L;Porter NA
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Porter NA
影响因子：
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Ayala A;Muñoz MF;Argüelles S
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Argüelles S
影响因子：
10.2
作者：
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通讯作者：
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影响因子：
4.7
作者：
Feigin, AM
通讯作者：
Feigin, AM