Dubertret et al., 2002; Gao et al., 2004; Larson et al., 2003; Lidke et al., 2004; Wu et al., 2003).
Traceable drug delivery has the potential to elucidate the pharmacokinetics and pharmacodynamics of drug candidates and to provide design principles for engineering drug carriers. Due to concerns about long-term in vivo toxicity and degradation, however, Qdots are currently limited to use in cells and small animals. However, because both cells and small animals are used extensively in testing drug candidates, even in these limited studies, traceable therapeutics have had a significant impact on life-science research, such as in drug discovery, validation, and delivery.
Following drug molecules or drug carriers noninvasively in real time in live organisms requires specialized imaging techniques. Compared with traditional imaging modalities, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), optical imaging is highly sensitive, quantitative, and capable of multiplexing. In addition, it is significantly cheaper than MRI and PET; thus it will substantially reduce the cost and shorten the time of new drug development. Therefore, for the development and optimization of nanocarriers, Qdots can be an excellent “prototype” from which biocompatible carriers of similar sizes and with similar surface properties can be made for clinical uses.
The importance of the structural properties of Qdots for drug-delivery research has only recently been realized. First, the size of Qdots can be continuously tuned from 2–10 nm in diameter, which, after polymer encapsulation, generally increases to 5–20 nm. Particles smaller than 5 nm are quickly cleared by renal filtration (Choi et al., 2007), whereas bigger particles are more likely to be taken up by the reticuloendothelial system before reaching the targeted disease sites. In addition, larger particles have limited penetration into solid tissues. Recent advances in Qdot nanocrystal synthesis will enable scientists to systematically assess the effects of size on delivery efficiency and specificity and identify the optimal dimensions of drug carriers.
Second, because of the high surface-to-volume ratio of nanomaterials, it is possible to link multiple functionalities on single Qdots while keeping the overall size in the optimal range. For example, the Qdot core can serve as the structural scaffold and the imaging contrast agent; and small-molecule hydrophobic drugs can be embedded between the inorganic core and the amphiphilic polymer coating. Hydrophilic therapeutic agents (e.g., small interfering RNA [siRNA] and antisense oligodeoxynucleotide [ODN]) and targeting biomolecules (e.g., antibodies, peptides, and aptamers), in turn, can be immobilized onto the hydrophilic side of the amphiphilic polymer via either covalent or noncovalent bonds. The fully integrated nanostructure may behave like a magic bullet that not only can