Compact Biocompatible Quantum Dots via RAFT-Mediated Synthesis of Imidazole-Based Random Copolymer Ligand

被引:235
作者
Liu, Wenhao [1 ]
Greytak, Andrew B. [1 ]
Lee, Jungmin [1 ]
Wong, Cliff R. [1 ]
Park, Jongnam [1 ]
Marshall, Lisa F. [1 ]
Jiang, Wen [2 ,3 ]
Curtin, Peter N. [1 ]
Ting, Alice Y. [1 ]
Nocera, Daniel G. [1 ]
Fukumura, Dai [2 ,3 ]
Jain, Rakesh K. [2 ,3 ]
Bawendi, Moungi G. [1 ]
机构
[1] MIT, Dept Chem, Cambridge, MA 02139 USA
[2] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
基金
美国国家科学基金会;
关键词
SEMICONDUCTOR NANOCRYSTALS; SURFACE MODIFICATION; SIZE SERIES; CDSE; LUMINESCENT; MONOVALENT; PROTEINS; CELLS; ADSORPTION; RECEPTORS;
D O I
10.1021/ja908137d
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We present a new class of polymeric ligands for quantum dot (OD) water solubilization to yield biocompatible and derivatizable QDs with compact size (similar to 10-12 nm diameter), high quantum yields (>50%), excellent stability across a large pH range (pH 5-10.5), and low nonspecific binding. To address the fundamental problem of thiol instability in traditional ligand exchange systems, the polymers here employ a stable multidentate imidazole binding motif to the OD surface. The polymers are synthesized via reversible addition-fragmentation chain transfer-mediated polymerization to produce molecular weight controlled monodisperse random copolymers from three types of monomers that feature imidazole groups for CID binding, polyethylene glycol (PEG) groups for water solubilization, and either primary amines or biotin groups for derivatization. The polymer architecture can be tuned by the monomer ratios to yield aqueous QDs with targeted surface functionalities. By incorporating amino-PEG monomers, we demonstrate covalent conjugation of a dye to form a highly efficient QD-dye energy transfer pair as well as covalent conjugation to streptavidin for high-affinity single molecule imaging of biotinylated receptors on live cells with minimal nonspecific binding. The small size and low serum binding of these polymer-coated QDs also allow us to demonstrate their utility for in vivo imaging of the tumor microenvironment in live mice.
引用
收藏
页码:472 / 483
页数:12
相关论文
共 52 条
[1]   Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols [J].
Aldana, J ;
Wang, YA ;
Peng, XG .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (36) :8844-8850
[2]   Adsorption and hybridization of oligonucleotides on mercaptoacetic acid-capped CdSe/ZnS quantum dots and quantum dot-oligonucleotide conjugates [J].
Algar, W. Russ ;
Krull, Ulrich J. .
LANGMUIR, 2006, 22 (26) :11346-11352
[3]   InAs(ZnCdS) Quantum Dots Optimized for Biological Imaging in the Near-Infrared [J].
Allen, Peter M. ;
Liu, Wenhao ;
Chauhan, Vikash P. ;
Lee, Jungmin ;
Ting, Alice Y. ;
Fukumura, Dai ;
Jain, Rakesh K. ;
Bawendi, Moungi G. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (02) :470-+
[4]   Noninvasive imaging of quantum dots in mice [J].
Ballou, B ;
Lagerholm, BC ;
Ernst, LA ;
Bruchez, MP ;
Waggoner, AS .
BIOCONJUGATE CHEMISTRY, 2004, 15 (01) :79-86
[5]  
BarnerKowollik C., 2008, Handbook of RAFT Polymerization
[6]   Surface modification to reduce nonspecific binding of quantum dots in live cell assays [J].
Bentzen, EL ;
Tomlinson, ID ;
Mason, J ;
Gresch, P ;
Warnement, MR ;
Wright, D ;
Sanders-Bush, E ;
Blakely, R ;
Rosenthal, SJ .
BIOCONJUGATE CHEMISTRY, 2005, 16 (06) :1488-1494
[7]   In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy [J].
Brown, EB ;
Campbell, RB ;
Tsuzuki, Y ;
Xu, L ;
Carmeliet, P ;
Fukumura, D ;
Jain, RK .
NATURE MEDICINE, 2001, 7 (07) :864-868
[8]   Semiconductor nanocrystals as fluorescent biological labels [J].
Bruchez, M ;
Moronne, M ;
Gin, P ;
Weiss, S ;
Alivisatos, AP .
SCIENCE, 1998, 281 (5385) :2013-2016
[9]   Living free-radical polymerization by reversible addition-fragmentation chain transfer: The RAFT process [J].
Chiefari, J ;
Chong, YK ;
Ercole, F ;
Krstina, J ;
Jeffery, J ;
Le, TPT ;
Mayadunne, RTA ;
Meijs, GF ;
Moad, CL ;
Moad, G ;
Rizzardo, E ;
Thang, SH .
MACROMOLECULES, 1998, 31 (16) :5559-5562
[10]   (CdSe)ZnS core-shell quantum dots: Synthesis and characterization of a size series of highly luminescent nanocrystallites [J].
Dabbousi, BO ;
RodriguezViejo, J ;
Mikulec, FV ;
Heine, JR ;
Mattoussi, H ;
Ober, R ;
Jensen, KF ;
Bawendi, MG .
JOURNAL OF PHYSICAL CHEMISTRY B, 1997, 101 (46) :9463-9475