The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging.
The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging.
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DOI：
10.1021/nn301630n
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发表时间：
2012-06-26
期刊：
影响因子：
17.1
通讯作者：
Davies, Catharina de Lange
中科院分区：
文献类型：
--
作者：
Hak, Sjoerd;Helgesen, Emily;Hektoen, Helga H.;Huuse, Else Marie;Jarzyna, Peter A.;Mulder, Willem J. M.;Haraldseth, Olav;Davies, Catharina de Lange
关键词：
纳米粒子作为治疗剂和/或诊断剂的体内递送载体的开发和应用在过去几十年中出现了急剧增长。新颖的成像技术允许在细胞和目标组织水平上实时体内研究纳米颗粒积累动力学。此类纳米载体的成功静脉应用需要亲水性颗粒表面涂层，其中聚乙二醇（PEG）已成为研究和应用最广泛的。在当前的研究中，研究了纳米颗粒PEG表面密度对配体功能化纳米乳液靶向效率的影响。我们合成了 100 nm 的纳米乳液，其 PEG 表面密度为 5 至 50 mol%。其中包含荧光和顺磁脂质以实现多模式检测，而 RGD 肽与 PEG 涂层缀合以获得 αvβ3 整合素的特异性。独特的实验成像装置的开发使我们能够利用共聚焦显微镜成像在窗室模型中生长的肿瘤中以（亚）细胞分辨率实时研究纳米粒子积累动力学，并利用磁共振成像在皮下生长的异种移植物中研究宏观肿瘤水平。与非靶向纳米乳液相比，靶向纳米乳液在肿瘤中的积累发生得更快，并且 PEG 表面密度对纳米颗粒靶向效率有很大影响。与直觉相反，但与 PEG 密度构象模型一致，在低 PEG 表面密度下观察到最高的特异性和靶向效率。
The development and application of nanoparticles as in vivo delivery vehicles for therapeutic and/or diagnostic agents has seen a drastic growth over the last decades. Novel imaging techniques allow real-time in vivo study of nanoparticle accumulation kinetics at the level of the cell and targeted tissue. Successful intravenous application of such nanocarriers requires a hydrophilic particle surface coating, of which polyethylene glycol (PEG) has become the most widely studied and applied. In the current study, the effect of nanoparticle PEG surface density on the targeting efficiency of ligand-functionalized nanoemulsions was investigated. We synthesized 100 nm nanoemulsions with a PEG surface density varying from 5 to 50 mol%. Fluorescent and paramagnetic lipids were included to allow their multimodal detection, while RGD peptides were conjugated to the PEG coating to obtain specificity for the αvβ3-integrin. The development of a unique experimental imaging setup allowed us to study, in real time, nanoparticle accumulation kinetics at (sub)-cellular resolution in tumors that were grown in a window chamber model with confocal microscopy imaging, and at the macroscopic tumor level in subcutaneously grown xenografts with magnetic resonance imaging. Accumulation in the tumor occurred more rapidly for the targeted nanoemulsions than for the non-targeted versions, and the PEG surface density had a strong effect on nanoparticle targeting efficiency. Counter intuitively, yet consistent with the PEG density conformation models, the highest specificity and targeting efficiency was observed at a low PEG surface density.
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DOI：
10.1002/wnan.72
发表时间：
2010-03
影响因子：
8.6
作者：
Jarzyna, Peter A.;Gianella, Anita;Skajaa, Torjus;Knudsen, Gitte;Deddens, Lisette H.;Cormode, David P.;Fayad, Zahi A.;Mulder, Willem J. M.
通讯作者：
Mulder, Willem J. M.
影响因子：
3.8
作者：
Ashok, B;Arleth, L;Önyüksel, H
通讯作者：
Önyüksel, H
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
5.8
作者：
Georgiev, Georgi As.;Sarker, Dipak K.;Lalchev, Zdravko
通讯作者：
Lalchev, Zdravko
影响因子：
5.8
作者：
Essa, Sherief;Rabanel, Jean Michel;Hildgen, Patrice
通讯作者：
Hildgen, Patrice