Anal. Chem., 80 (8), 3029 -3034, 2008. 10.1021/ac800068q S0003-2700(80)00068-6
Web Release Date: March 7, 2008

Copyright © 2008 American Chemical Society

Minimizing Nonspecific Cellular Binding of Quantum Dots with Hydroxyl-Derivatized Surface Coatings

Brad A. Kairdolf, Michael C. Mancini, Andrew M. Smith, and Shuming Nie*

Departments of Biomedical Engineering and Chemistry, Emory University and Georgia Institute of Technology, 101 Woodruff Circle, Suite 2001, Atlanta, Georgia 30322

Received for review January 10, 2008. Accepted January 30, 2008.

Abstract:

Quantum-dot (QD) nanocrystals are promising fluorescent probes for multiplexed staining assays in biological applications. However, nonspecific QD binding to cellular membranes and proteins remains a limiting factor in detection sensitivity and specificity. Here we report a new class of hydroxyl (-OH)-coated QDs for minimizing nonspecific cellular binding and for overcoming the bulky size problems encountered with previous surface coatings. The hydroxylated QDs are prepared from carboxylated (-COOH) dots via a hydroxylation and cross-linking process. With a compact hydrodynamic size of 13-14 nm (diameter), they are highly fluorescent (>60% quantum yields) and stable under both basic and acidic conditions. By using human cancer cells, we have evaluated their superior nonspecific binding properties against that of carboxylated, protein-coated, and poly(ethylene glycol) (PEG)-coated QDs. Quantitative cellular staining data indicate that the hydroxylated QDs result in a dramatic 140-fold reduction in nonspecific binding relative to that of carboxylated dots and a still significant 10-20-fold reduction relative to that of PEG- and protein-coated dots.


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