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 (approximately 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.
Liu
Wenhao
W
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge Massachusetts 02139-4307, USA.
Greytak
Andrew B
AB
Lee
Jungmin
J
Wong
Cliff R
CR
Park
Jongnam
J
Marshall
Lisa F
LF
Jiang
Wen
W
Curtin
Peter N
PN
Ting
Alice Y
AY
Nocera
Daniel G
DG
Fukumura
Dai
D
Jain
Rakesh K
RK
Bawendi
Moungi G
MG
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D015394:Molecular Structure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D045663:Quantum Dots; D013499:Surface Properties
D001672:Biocompatible Materials; D007093:Imidazoles; D008024:Ligands; D011092:Polyethylene Glycols; C029899:imidazole