Compact biocompatible quantum dots via RAFT-mediated synthesis of imidazole-based random copolymer ligand.

Compact biocompatible quantum dots via RAFT-mediated synthesis of imidazole-based random copolymer ligand.
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DOI:
10.1021/ja908137d
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发表时间:
2010-01-20
影响因子:
15
通讯作者:
Bawendi, Moungi G.
Bawendi, Moungi G.
中科院分区:
化学1区
文献类型:
--
作者:
Liu, Wenhao;Greytak, Andrew B.;Lee, Jungmin;Wong, Cliff R.;Park, Jongnam;Marshall, Lisa F.;Jiang, Wen;Curtin, Peter N.;Ting, Alice Y.;Nocera, Daniel G.;Fukumura, Dai;Jain, Rakesh K.;Bawendi, Moungi G.

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我们提出了一类新的用于量子点(QD)水增溶的聚合物配体,以产生具有紧凑尺寸(约10-12 nm直径)、高量子产率(>50%)、在大pH范围(pH 5-10.5)内优异的稳定性和低非特异性结合的生物相容性和可衍生的QD。为了解决传统配体交换系统中硫醇不稳定的根本问题,这里的聚合物采用稳定的多齿咪唑结合基序到QD表面。通过可逆加成-断裂链转移(RAFT)介导的聚合来合成聚合物,以从三种类型的单体产生分子量受控的单分散无规共聚物,所述三种类型的单体具有用于QD结合的咪唑基团、用于水增溶的聚乙二醇(PEG)基团以及用于衍生化的伯胺或生物素基团。聚合物结构可以通过单体比例来调节,以产生具有目标表面官能团的水性QD。通过掺入氨基-PEG单体,我们证明了染料的共价缀合以形成高效的QD-染料能量转移对以及与链霉亲和素的共价缀合,用于以最小的非特异性结合对活细胞上的生物素化受体进行高亲和力单分子成像。这些聚合物涂层量子点的小尺寸和低血清结合也使我们能够证明它们对于活小鼠肿瘤微环境体内成像的实用性。
We present a new class of polymeric ligands for quantum dot (QD) water solubilization to yield biocompatible and derivatizable QDs with compact size (~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 QD surface. The polymers are synthesized via reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization to produce molecular weight controlled monodisperse random copolymers from three types of monomers that feature imidazole groups for QD 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 non-specific 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.
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