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A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia 期刊论文

编号：

107496a0-7340-4a88-9be7-9cc6b2df0656
作者：

Luan, Xin#^[1,2,3,4]Guan, YingYun#^[1,2,5]Liu, HaiJun^[1,2];Lu, Qin^[1,2];Zhao, Mei(赵梅)^[6]Sun, Duxin^[3];Lovell, Jonathan F.^[7];Sun, Peng^[8];Chen, HongZhuan*^[1,2,4]Fang, Chao*^[1,2]
语种：

英文
期刊：

ADVANCED SCIENCE ISSN：2198-3844 2018 年 5 卷 8 期 ; AUG
收录：
关键词：

graphene oxide hypoxia-activated prodrug photodynamic therapy trimodal therapy tumor hypoxia
摘要：

Vascular-targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)-based nanosystem for rationally designed, interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxia-activated prodrug (HAP), and HIF-1 siRNA (siHIF-1) (3) is reported. The VTP-induced aggravated hypoxia is highly favorable for AQ4N activation into AQ4 (a topoisomerase II inhibitor) for chemotherapy. However, the hypoxia-induced HIF-1 acts as a hidden brake, through downregulating CYP450 (the dominant HAP-activating reductases), to substantially hinder AQ4N activation. siHIF-1 is rationally adopted to suppress the HIF-1 expression upon hypoxia and further enhance AQ4N activation. This trimodal nanosystem significantly delays the growth of PC-3 tumors in vivo compared to the control nanoparticles carrying VP, AQ4N, or siHIF-1 alone or their pairwise combinations. This multimodal nanoparticle design presents, the first example exploiting VTP to actively induce hypoxia for enhanced HAP activation. It is also revealed that HAP activation is still insufficient under hypoxia due to the hidden downregulation of the HAP-activating reductases (CYP450), and this can be well overcome by GO nanoparticle-mediated siHIF-1 intervention.
推荐引用方式
GB/T 7714：

Luan Xin,Guan Ying-Yun,Liu Hai-Jun, et al. A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia [J].ADVANCED SCIENCE,2018,5(8).
APA：

Luan Xin,Guan Ying-Yun,Liu Hai-Jun,Lu Qin,&Fang Chao.(2018).A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia .ADVANCED SCIENCE,5(8).
MLA：

Luan Xin, et al. "A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia" .ADVANCED SCIENCE 5,8(2018).
入库时间：

10/23/2019 2:37:08 PM
更新时间：

10/23/2019 2:37:08 PM
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