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

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 th...

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Bibliographic Details
Main Authors: Liu, Wenhao, Greytak, Thomas J., Lee, Jungmin, Wong, Cliff, Park, Jongnam, Marshall, Lisa Faye, Jiang, Wen, Curtin, Peter N., Ting, Alice Y., Nocera, Daniel G., Fukumura, Dai, Jain, Rakesh K., Bawendi, Moungi G.
Other Authors: Massachusetts Institute of Technology. Department of Chemistry
Format: Article
Language:en_US
Published: American Chemical Society 2012
Online Access:http://hdl.handle.net/1721.1/73650
https://orcid.org/0000-0003-2220-4365
https://orcid.org/0000-0002-8277-5226
https://orcid.org/0000-0002-4507-1115
https://orcid.org/0000-0001-9769-2418
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Summary: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-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 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.