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Reversible Electroporation-Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With 89Zr-Labeled Reporter Nanoparticles.
Molecular Imaging ( IF 2.8 ) Pub Date : 2018-02-27 , DOI: 10.1177/1536012117749726
Govindarajan Srimathveeravalli 1, 2 , Dalya Abdel-Atti 1 , Carlos Pérez-Medina 3 , Haruyuki Takaki 4 , Stephen B Solomon 1, 2 , Willem J M Mulder 3, 5 , Thomas Reiner 1, 2
Affiliation  

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation-related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep.

中文翻译:

可逆电穿孔介导的脂质体阿霉素递送至肿瘤可用89Zr标签的记者纳米颗粒监测。

可逆电穿孔(RE)可通过直接转染和血管通透性变化促进纳米颗粒向肿瘤的递送。我们调查了放射性标记的脂质体纳米颗粒(89Zr-NRep),以监测RE介导的脂质体阿霉素(DOX)在小鼠肿瘤中的递送。静脉内递送的89Zr-NRep允许正电子发射断层显像成像对电穿孔介导的纳米颗粒摄取进行成像。89Zr-NRep注射和电穿孔的相对顺序并未导致总体肿瘤摄取发生显着差异,这表明直接转染和血管通透性可以独立介导肿瘤中89Zr-NRep的沉积。在所有实验时间点,在电穿孔和对照肿瘤中,89Zr-NRep和DOX摄取均具有良好的相关性。电穿孔加速了89Zr-NRep和DOX在肿瘤中的沉积,并增加了DOX剂量。可逆的与电穿孔相关的血管作用似乎在纳米颗粒向肿瘤的传递中起着重要作用,并且可以使用89Zr-NRep量化药物的吸收。
更新日期:2019-11-01
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