The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line

被引:288
作者
Clift, Martin J. D. [1 ]
Rothen-Rutishauser, Barbara [2 ]
Brown, David M. [1 ]
Duffin, Rodger [3 ]
Donaldson, Ken [3 ]
Proudfoot, Lorna [1 ]
Guy, Keith [1 ]
Stone, Vicki [1 ]
机构
[1] Napier Univ, Sch Life Sci, Appl Res Ctr Hlth Environm & Soc, Biomed & Sport Sci Res Grp, Edinburgh EH10 5DT, Midlothian, Scotland
[2] Univ Bern, Div Histol, Inst Anat, CH-3000 Bern 9, Switzerland
[3] Univ Edinburgh, Queens Med Res Inst, Ctr Inflammat Res, ELEGI Colt Lab, Edinburgh EH16 4TJ, Midlothian, Scotland
基金
英国医学研究理事会;
关键词
Surface coating; Quantum dots (QDs); Polystyrene beads (PBs); J774.A1; macrophages; Nanoparticles (NPs); Confocal microscopy; Cellular uptake; Fluorescent stability; Toxicity;
D O I
10.1016/j.taap.2008.06.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study investigated the uptake, kinetics and cellular distribution of different surface coated quantum dots (QDs) before relating this to their toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads (PBs) were also examined (50 mu g ml(-1)). The potential for uptake of QDs was examined by both fixed and live cell confocal microscopy as well as by flow cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages. Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was observed following 3D reconstruction of fixed cells, as well as by flow cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed only a small amount of uptake in a relatively small number of cells. This uptake was insufficient to be detected by flow cytometry. Imaging of fixed cells was not possible due to a loss in cell integrity related to cytotoxicity. A significant reduction (p < 0.05) in the fluorescent intensity in a cell-free environment was found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative of an endosome) after 2 h, suggesting reduced stability. No evidence of exocytosis was found over 2 h. These findings confirm that surface coating has a significant influence on the mode of NP interaction with cells, as well as the subsequent consequences of that interaction. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:418 / 427
页数:10
相关论文
共 43 条
[1]   Nanocrystal targeting in vivo [J].
Åkerman, ME ;
Chan, WCW ;
Laakkonen, P ;
Bhatia, SN ;
Ruoslahti, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12617-12621
[2]  
[Anonymous], NAN ESF EUR MED RES
[3]   Nanodiagnostics: A new frontier for clinical laboratory medicine [J].
Azzazy, Hassan M. E. ;
Mansour, Mai M. H. ;
Kazmierczak, Steven C. .
CLINICAL CHEMISTRY, 2006, 52 (07) :1238-1246
[4]   Quantum dots in biology and medicine [J].
Bailey, RE ;
Smith, AM ;
Nie, SM .
PHYSICA E-LOW-DIMENSIONAL SYSTEMS & NANOSTRUCTURES, 2004, 25 (01) :1-12
[5]   Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens [J].
Blank, Fabian ;
Rothen-Rutishauser, Barbara ;
Gehr, Peter .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2007, 36 (06) :669-677
[6]   Size-dependent proinflammatory effects of ultrafine polystyrene particles: A role for surface area and oxidative stress in the enhanced activity of ultrafines [J].
Brown, DM ;
Wilson, MR ;
MacNee, W ;
Stone, V ;
Donaldson, K .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2001, 175 (03) :191-199
[7]   Nanotechnological applications in medicine [J].
Caruthers, Shelton D. ;
Wickline, Samuel A. ;
Lanza, Gregory M. .
CURRENT OPINION IN BIOTECHNOLOGY, 2007, 18 (01) :26-30
[8]   Quantum dot bioconjugates for ultrasensitive nonisotopic detection [J].
Chan, WCW ;
Nie, SM .
SCIENCE, 1998, 281 (5385) :2016-2018
[9]  
Derfus AM, 2004, NANO LETT, V4, P11, DOI 10.1021/nl0347334
[10]   Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings [J].
Duan, Hongwei ;
Nie, Shuming .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (11) :3333-3338