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Biomolecules/Nanoparticles

Quantum dots possess the unique property of size-tunable emission upon UV excitation.
W. Chan/S. Nie

Fluorescent semiconductor nanocrystals or ‘quantum dots' show promise as alternatives to organic dyes for biological labeling. Qdots are generally composed of atoms from groups II–VI or III–V of the periodic table and are defined as particles with physical dimensions smaller than the exciton Bohr radius. This size leads to a quantum confinement effect, which endows nanocrystals with unique optical and electronic properties. Qdots have size-tunable emission (from the ultraviolet to the infrared), narrow spectral line widths, high luminescence, continuous absorption profiles, and stability against photobleaching. Furthermore, the large surface area-to-volume ratio of qdots makes them appealing for the design of more complex nanobiological systems. We have explored both in vivo (tumor targeting) and in vitro (live cell imaging) applications of these nanoparticles by investigating strategies for bioconjugation and cellular delivery. By coupling both homing peptides and nonfouling polymers to the qdot surface, we have demonstrated the ability to target qdots to tumor endothelium in vivo Akerman & Chan et al (2002), PNAS . The figure below schematically depicts the experiments performed in this paper. Furthermore, by coupling canonical localization sequences to the particles, we have shown that the cell will actively traffic these bioconjugates to subcellular organelles (nucleus, mitochondria) Derfus et al (2004). Adv. Mat. We are expanding this work to target multimodal nanodevices of varying size, composition, and functionality to enable detection, imaging, and drug delivery.

Schematic representation of qdot targeting. Intravenous delivery of
qdots into specific tissues of the mouse. (Upper) Design of peptide-coated
qdots. (Lower) Qdots were coated with either peptides only or with peptides
and PEG. PEG helps the qdots maintain solubility in aqueous solvents and
minimize nonspecific binding.
Akerman & Chan et al (2002), PNAS .

Subcellular localization of QDS. PEG-QDs were conjugated to localization sequence peptides, which permit active transport to the nucleus or mitochondria. Here, fluorescence and phase contrast micrographs of a HeLa cell 24 hr after co-injection of NLS-QDs with 70kDa rhodamine dextran control. Derfus et al (2004). Adv. Mat.

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