Zwitterionand Oligo(ethylene glycol) Synergy MinimizesNonspecific Binding of Compact Quantum Dots
2020
Quantum
dots (QDs) are a class of fluorescent nanocrystals in development
as labels for molecular imaging in cells and tissues. Recently, coatings
for quantum dots based on multidentate polymers have improved labeling
performance in a range of bioanalytical applications, primarily due
to reduced probe hydrodynamic size. Now, an ongoing challenge is to
eliminate nonspecific binding between these small probes and cellular
components that mask specifically labeled molecules. Here, we describe
insights into controlling and minimizing intermolecular interactions
governing nonspecific binding using multidentate polymers with tunable
hydrophilic functional groups that are cationic, anionic, zwitterionic
(ZW), or nonionic (oligoethylene glycol; OEG). By fixing surface-binding
groups and polymer length, coated colloids have similar sizes but
diverse physicochemical properties. We measure binding to globular
proteins, fixed cells, and living cells and observe a substantial
improvement in nonspecific binding resistance when surfaces are functionalized
with a combination of ZW and OEG. The independent underlying effects
of counterion adsorption and flexibility appear to synergistically
resist adsorption when combined, particularly for fixed cells enriched
in both charged and hydrophobic moieties. We further show that ZW-OEG
QDs are stable under diverse conditions and can be self-assembled
with antibodies to specifically label surface antigens on living cells
and cytoplasmic proteins in fixed cells. This surface engineering
strategy can be adopted across the diverse range of colloidal materials
currently in use and in development for biomedical applications to
optimize their molecular labeling specificity.
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