Due to their novel optical and electronic properties, semiconductor QDs are being intenselystudied as a new class of nanoparticle probe for molecular, cellular, and
imaging [10–24]. Over the past decade, researchers have generated highly monodispersed QDs encapsulatedin stable polymers with versatile surface chemistries. These nanocrystals are brightlyfluorescent, enabling their use as imaging probes both
. In this article, wediscuss recent developments in the synthesis and modification of QD nanocrystals, and theiruse as imaging probes for living cells and animals. We also discuss the use of QDs as ananoscale carrier to develop multifunctional nanoparticles for integrated imaging and therapy.In addition, we describe QD biodistribution, pharmacokinetics, toxicology, as well as thechallenges and opportunities in developing nanoparticle agents for
imaging and therapy.
2. QD Chemistry and Probe Development
QDs are nearly spherical semiconductor particles with diameters on the order of 2–10nanometers, containing roughly 200–10,000 atoms. The semiconducting nature and the size-dependent fluorescence of these nanocrystals have made them very attractive for use inoptoelectronic devices, biological detection, and also as fundamental prototypes for the studyof colloids and the size-dependent properties of nanomaterials . Bulk semiconductors arecharacterized by a composition-dependent bandgap energy, which is the minimum energyrequired to excite an electron to an energy level above its ground state, commonly through theabsorption of a photon of energy greater than the bandgap energy. Relaxation of the excitedelectron back to its ground state may be accompanied by the fluorescent emission of a photon.Small nanocrystals of semiconductors are characterized by a bandgap energy that is dependenton the particle size, allowing the optical characteristics of a QD to be tuned by adjusting itssize. Figure 1 shows the optical properties of CdSe QDs at four different sizes (2.2 nm, 2.9nm, 4.1 nm, and 7.3 nm). In comparison with organic dyes and fluorescent proteins, QDs areabout 10–100 times brighter, mainly due to their large absorption cross sections, 100–1000times more stable against photobleaching, and show narrower and more symmetric emissionspectra. In addition, a single light source can be used to excite QDs with different emissionwavelengths, which can be tuned from the ultraviolet , throughout the visible and near-infrared spectra [30–33], and even into the mid-infrared . However QDs aremacromolecules that are an order of magnitude larger than organic dyes, which may limit theiruse in applications in which the size of the fluorescent label must be minimized. Yet, thismacromolecular structure allows the QD surface chemistry and biological functionality to bemodified independently from its optical properties.
2.1. QD Synthesis
QD synthesis was first described in 1982 by Efros and Ekimov [35,36], who grew nanocrystalsand microcrystals of semiconductors in glass matrices. Since this work, a wide variety of synthetic methods have been devised for the preparation of QDs in different media, includingaqueous solution, high-temperature organic solvents, and solid substrates [28,37,38]. Colloidalsuspensions of QDs are commonly synthesized through the introduction of semiconductorprecursors under conditions that thermodynamically favor crystal growth, in the presence of semiconductor-binding agents, which function to kinetically control crystal growth andmaintain their size within the quantum-confinement size regime.The size-dependent optical properties of QDs can only be harnessed if the nanoparticles areprepared with narrow size distributions. Major progress toward this goal was made in 1993 byBawendi and coworkers , with the introduction of a synthetic method for monodisperseQDs made from cadmium sulfide (CdS), cadmium selenide (CdSe), or cadmium telluride(CdTe). Following this report, the synthetic chemistry of CdSe QDs quickly advanced,generating brightly fluorescent QDs that can span the visible spectrum. As a result, CdSe hasbecome the most common chemical composition for QD synthesis, especially for biological
Smith et al.Page 2
Adv Drug Deliv Rev
. Author manuscript; available in PMC 2009 August 17.
N I H -P A A u t h or M an u s c r i p t N I H -P A A u t h or M an u s c r i p t N I H -P A A u t h or M an u s c r i p t