Nanoparticle-mediated knockdown of DNA repair sensitizes cells to radiotherapy and extends survival in a genetic mouse model of glioblastoma.
Nanoparticle-mediated knockdown of DNA repair sensitizes cells to radiotherapy and extends survival in a genetic mouse model of glioblastoma.
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DOI：
10.1016/j.nano.2017.06.004
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Kievit FM;Wang K;Ozawa T;Tarudji AW;Silber JR;Holland EC;Ellenbogen RG;Zhang M
胶质母细胞瘤(GBM)仍然是无法治愈的，复发的肿瘤很少对标准的放化疗有反应。因此，加强这些治疗效果的策略应该会为GBM患者提供显著的好处。我们已经开发了一种纳米颗粒递送载体，可以稳定地结合和保护特定递送到脑瘤细胞的核酸。这些纳米粒子可以传递治疗性的siRNA，使GBM细胞对放射治疗敏感，并通过全身给药改善GBM的治疗。我们发现，纳米颗粒介导的DNA修复蛋白无嘌呤核酸内切酶1(APE1)的敲除使GBM细胞对放射治疗敏感，并延长了GBM遗传性小鼠模型的生存时间。脑肿瘤组织中APE1活性的特异性下调30%使单纯放射治疗的延长生存期翻了一番。APE1是提高放射治疗效果的一个有前景的靶点，而纳米颗粒介导的siRNA传递是一种有希望的肿瘤特异性APE1基因敲除策略。
Glioblastoma (GBM) remains incurable, and recurrent tumors that rarely respond to standard-of-care radiation and chemo therapies. Therefore, strategies that enhance the effects of these therapies should provide significant benefits to GBM patients. We have developed a nanoparticle delivery vehicle that can stably bind and protect nucleic acids for specific delivery into brain tumor cells. These nanoparticles can deliver therapeutic siRNAs to sensitize GBM cells to radiotherapy and improve GBM treatment via systemic administration. We show that nanoparticle-mediated knockdown of the DNA repair protein apurinic endonuclease 1 (Ape1) sensitizes GBM cells to radiotherapy and extend survival in a genetic mouse model of GBM. Specific knockdown of Ape1 activity by 30% in brain tumor tissue doubled the extended survival achieved with radiotherapy alone. Ape1 is a promising target for increasing the effectiveness of radiotherapy, and nanoparticle-mediated delivery of siRNA is a promising strategy for tumor specific knockdown of Ape1.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
17.1
作者：
Kievit FM;Veiseh O;Fang C;Bhattarai N;Lee D;Ellenbogen RG;Zhang M
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Zhang M
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
64.5
作者：
Leder K;Pitter K;LaPlant Q;Hambardzumyan D;Ross BD;Chan TA;Holland EC;Michor F
通讯作者：
Michor F
影响因子：
11.5
作者：
Bobola, MS;Finn, LS;Silber, JR
通讯作者：
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