The Effect of Nanoparticle Polyethylene Glycol Surface Density on Ligand-Directed Tumor Targeting Studied in Vivo by Dual Modality Imaging

被引:166
作者
Hak, Sjoerd [1 ,2 ]
Helgesen, Emily [3 ]
Hektoen, Helga H. [3 ]
Huuse, Else Marie [1 ,2 ]
Jarzyna, Peter A. [4 ,5 ]
Mulder, Willem J. M. [4 ,5 ]
Haraldseth, Olav [1 ,2 ,4 ,5 ]
Davies, Catharina de Lange [3 ]
机构
[1] Norwegian Univ Sci & Technol, MI Lab, N-7034 Trondheim, Norway
[2] Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, N-7034 Trondheim, Norway
[3] Norwegian Univ Sci & Technol, Dept Phys, N-7034 Trondheim, Norway
[4] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY USA
[5] St Olavs Univ Hosp, Dept Med Imaging, Trondheim, Norway
关键词
nanoemulsion; targeting-ligand; polyethylene glycol; surface density; intravital microscopy; dorsal window chamber; DCE-MRI; POLYPLEX MICELLES; LIPOSOMES; VASCULATURE; PEGYLATION; CAVEOLAE; SIZE; TIME;
D O I
10.1021/nn301630n
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 alpha(v)beta(3)-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 nontargeted versions, and the PEG surface density had a strong effect on nanoparticle targeting efficiency. Counterintuitively, yet consistent with the PEG density conformation models, the highest specificity and targeting efficiency was observed at a low PEG surface density.
引用
收藏
页码:5648 / 5658
页数:11
相关论文
共 45 条
[1]   Multifunctional Nanoparticles for Dual Imaging [J].
Ali, Z. ;
Abbasi, A. Z. ;
Zhang, F. ;
Arosio, P. ;
Lascialfari, A. ;
Casula, M. F. ;
Wenk, A. ;
Kreyling, W. ;
Plapper, R. ;
Seidel, M. ;
Niessner, R. ;
Knoell, J. ;
Seubert, A. ;
Parak, W. J. .
ANALYTICAL CHEMISTRY, 2011, 83 (08) :2877-2882
[2]   In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization:: Effects of PEG chain length and PC incorporation [J].
Ashok, B ;
Arleth, L ;
Hjelm, RP ;
Rubinstein, I ;
Önyüksel, H .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2004, 93 (10) :2476-2487
[3]   Imaging of integrin αvβ3 expression [J].
Beer, Ambros J. ;
Schwaiger, Markus .
CANCER AND METASTASIS REVIEWS, 2008, 27 (04) :631-644
[4]  
Bhadra D, 2002, PHARMAZIE, V57, P5
[5]   REQUIREMENT OF VASCULAR INTEGRIN ALPHA(V)BETA(3) FOR ANGIOGENESIS [J].
BROOKS, PC ;
CLARK, RAF ;
CHERESH, DA .
SCIENCE, 1994, 264 (5158) :569-571
[6]   Dual-function probe for PET and near-infrared fluorescence imaging of tumor vasculature [J].
Cai, Weibo ;
Chen, Kai ;
Li, Zi-Bo ;
Gambhir, Sanjiv S. ;
Chen, Xiaoyuan .
JOURNAL OF NUCLEAR MEDICINE, 2007, 48 (11) :1862-1870
[7]   Endocytic transport of integrins during cell migration and invasion [J].
Caswell, Patrick ;
Norman, Jim .
TRENDS IN CELL BIOLOGY, 2008, 18 (06) :257-263
[8]   Integrin trafficking and the control of cell migration [J].
Caswell, PT ;
Norman, JC .
TRAFFIC, 2006, 7 (01) :14-21
[9]   A biotechnological perspective on the application of iron oxide magnetic colloids modified with polysaccharides [J].
Dias, A. M. G. C. ;
Hussain, A. ;
Marcos, A. S. ;
Roque, A. C. A. .
BIOTECHNOLOGY ADVANCES, 2011, 29 (01) :142-155
[10]  
Erikson A, 2008, ANTICANCER RES, V28, P3557