DNA-templated assembly of a heterobivalent quantum dot nanoprobe for extra- and intracellular dual-targeting and imaging of live cancer cells.

Quantum dots (QDs) hold great promise for the molecular imaging of cancer because of their superior optical properties. Although cell-surface biomarkers can be readily imaged with QDs, non-invasive live-cell imaging of critical intracellular cancer markers with QDs is a great challenge because of the difficulties in the automatic delivery of QD probes to the cytosol and the ambiguity of intracellular targeting signals. Herein, we report a new type of DNA-templated heterobivalent QD nanoprobes with the ability to target and image two spatially isolated cancer markers (nucleolin and mRNA) present on the cell surface and in the cell cytosol. Bypassing endolysosomal sequestration, this type of QD nanoprobes undergo macropinocytosis following the nucleolin targeting and then translocate to the cytosol for mRNA targeting. Fluorescence resonance energy transfer (FRET) based confocal microscopy enables unambiguous signal deconvolution of mRNA-targeted QD nanoprobes inside cancer cells.