Selective cellular delivery of self-assembled quantum dot-peptide bioconjugates

Abstract

We demonstrate the selective delivery of self-assembled luminescent semiconductor quantum dot (QD)-peptide bioconjugates into several eukaryotic cell lines. A 23-mer hetero-bifunctional peptide bearing a positively-charged oligoarginine domain and a terminal polyhistidine tract was synthesized and used to mediate the cellular internalization of the QD-bioconjugates. The polyhistidine tract allows the peptide to self-assemble onto the QD surface via metal-ion coordination while the oligoarginine domain mediates the specific uptake of the QD-bioconjugates via electrostatic interactions with cell surface receptors. In both HEK 293T/17 and COS-1 cells, this peptide-mediated delivery is concentration-dependent in terms of both the QD concentration and the peptide:QD ratio. Intracellularly, the QD signal is punctate in appearance and some, but not all, of the QDs are located within recycling endosomes as evidenced by their colocalization with transferrin. In both cell lines, the QD-bioconjugates elicit minimal cytotoxicity within the timeframe required for adequate cellular uptake. The specificity of this delivery strategy is demonstrated by performing a multicolor QD labeling, wherein the presence or absence of the peptide on the QD surface controls cellular uptake.