Oxygen nanobubbles revert hypoxia by methylation programming.
Oxygen nanobubbles revert hypoxia by methylation programming.
复制标题
氧纳米泡通过甲基化编程恢复缺氧。
DOI：
10.1038/s41598-017-08988-7
复制
发表时间：
2017-08-24
影响因子：
4.6
通讯作者：
Irudayaraj J
中科院分区：
文献类型：
--
作者：
Bhandari PN;Cui Y;Elzey BD;Goergen CJ;Long CM;Irudayaraj J
靶向低氧肿瘤微环境在肿瘤表观遗传学和治疗学中具有广泛的影响。氧包被纳米级羧甲基纤维素纳米气泡被开发用于缓解肿瘤的缺氧区域，以削弱缺氧驱动通路并抑制肿瘤生长。在体外和体内实验中，我们发现肿瘤缺氧区域的5-甲基胞嘧啶（5mC）低甲基化可以通过表观遗传调控进行逆转，从而增强癌症治疗。氧纳米泡在小鼠模型中显著延缓肿瘤进展和提高生存率。此外，由于氧纳米泡（ONB）处理，在BRCA1的启动子DNA区域观察到显著的超甲基化。除了作为超声造影剂外，纳米气泡还可以重新编程几种与缺氧相关的肿瘤抑制基因，如MAT2A和PDK-1。我们的方法是开发纳米氧封装气泡作为甲基化逆转的超声造影剂，预计将对表观遗传编程产生重大影响，并作为癌症治疗的辅助手段。
Targeting the hypoxic tumor microenvironment has a broad impact in cancer epigenetics and therapeutics. Oxygen encapsulated nanosize carboxymethyl cellulosic nanobubbles were developed for mitigating the hypoxic regions of tumors to weaken the hypoxia-driven pathways and inhibit tumor growth. We show that 5-methylcytosine (5mC) hypomethylation in hypoxic regions of a tumor can be reverted to enhance cancer treatment by epigenetic regulation, using oxygen nanobubbles in the sub-100 nm size range, both, in vitro and in vivo. Oxygen nanobubbles were effective in significantly delaying tumor progression and improving survival rates in mice models. Further, significant hypermethylation was observed in promoter DNA region of BRCA1 due to oxygen nanobubble (ONB) treatment. The nanobubbles can also reprogram several hypoxia associated and tumor suppressor genes such as MAT2A and PDK-1, in addition to serving as an ultrasound contrast agent. Our approach to develop nanosized oxygen encapsulated bubbles as an ultrasound contrast agent for methylation reversal is expected to have a significant impact in epigenetic programming and to serve as an adjuvant to cancer treatment.
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DOI：
10.1038/nrclinonc.2013.42
发表时间：
2013-05
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.9
作者：
DOROSHOW, JH;LOCKER, GY;MYERS, CE
通讯作者：
MYERS, CE
影响因子：
2.8
作者：
Ghafar, MA;Anastasiadis, AG;Buttyan, R
通讯作者：
Buttyan, R
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
影响因子：
3
作者：
DORR, RT;ALBERTS, DS;CHEN, HSG
通讯作者：
CHEN, HSG