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Fractal Nanoplasmonic Labels for Super-Multiplex Imaging in Single Cells.

The rapidly increasing need for systems biology stimulates the development of super-multiplex (SM) methods for simultaneously labeling multiple biomolecules/cells with distinct colors. Here we report the development of DNA-engineered fractal nanoplasmonic labels with ultrahigh brightness and photostability for SM imaging in single cell. These color-resolvable nanoplasmonic labels have a uniform size of ~50 nm with an inner hollow gap of ~1 nm. The outer shell morphology is highly tunable with the tip aspect ratio covering the range of δ=0.29~1.66, which supports SM plasmonic imaging exceeding the conventional fluorescence multiplexing limit. We demonstrate the use of these SM labels for quantitative imaging of receptor-mediated endocytosis and intracellular transport of multiple protein-NP structures in a single cell in real time. This SM-plasmonic method sheds light on elucidating complex interactions among protein-NP in nanotoxicology and facilitates the development of novel nanomedicine for diagnosis and therapy.