Nanoparticle-based
cellular probes are commonly designed via covalent
conjugation with affinity biomolecules. Those nanobioconjugates selectively
interact with cell surface receptors and induce endocytosis followed
by intracellular trafficking. However, this approach requires functional
modification of biomolecules that may alter their biochemical activity.
Here, we show that supramolecular host–guest chemistry can
be utilized as an alternative approach in nanoparticle functionalization
and selective cell labeling. We have used cyclodextrin-conjugated
quantum dots (QDs) for supramolecular host–guest interaction-based
functionalization with folate (QD-folate) and riboflavin (QD-riboflavin),
where cyclodextrin acts as a host for the folate/riboflavin guest.
We demonstrate that QD-folate and QD-riboflavin selectively label
cells that have over-expressed folate/riboflavin receptors and induce
the endocytosis pathway similar to covalently conjugated folate-/riboflavin-based
nanoprobes. However, labeling is highly sensitive to the molar ratio
of folate/riboflavin to cyclodextrin and incubation time. The presented
functionalization/labeling approach is unique as it does not require
covalent conjugation and may be extended for in vivo targeting application
via simultaneous delivery of host and guest molecules.