ABSTRACT

Quantum dots (QDs) are fluorescent semiconductor nanocrystals that have a diameter in the range of 1-10 nm [1]. Due to the nanoscale size, which is comparable to electron delocalization length, QDs have unique physical properties that are nonexistent in individual atoms or bulk semiconductor solids. The so-called quantum confinement effect is observed, when one or more dimensions of a semiconductor are reduced under the Bohr exciton radius, which is typically a few nanometers [2]. It is possible to systematically control the electronic energy-level spacings because of the quantum confinement effect, and the wavelength of light emission can also be controlled by adjusting the size of the semiconductor. The emission wavelength of QDs can be controlled over a wide range of spanning regions from the ultraviolet, through the visible, into the infrared, by selecting and adjusting the size and compositions [3-6]. Due to a radiative recombination of

2.1 Semiconductor Nanocrystals .......................................................................... 43 2.1.1 Photonic Properties of Semiconductor Nanocrystals ......................... 43 2.1.2 Synthesis of QDs ................................................................................44 2.1.3 Strategy for Aqueous Soluble QDs ..................................................... 45 2.1.4 Surface Modifications of QDs ............................................................ 45

2.2 Biological Applications of QDs ......................................................................46 2.2.1 Labeling of Cells.................................................................................46 2.2.2 Targeting of Intracellular Organelles ................................................. 49 2.2.3 Targeting of Specific Cells.................................................................. 53 2.2.4 Multiplexed Detection and Imaging ................................................... 55 2.2.5 Novel Applications of QDs ................................................................. 59

2.3 Medical Applications of QDs ......................................................................... 62 2.3.1 Cancer Diagnosis ................................................................................ 62 2.3.2 Cancer Therapy...................................................................................64 2.3.3 Other Applications (Multimodal Imaging) ........................................ 70

Acknowledgments .................................................................................................... 75 References ................................................................................................................ 75

an exciton, the emission of QDs is also characterized by a long lifetime (>10 ns), and a narrow and symmetric energy band [7]. Compared with the traditional fluorescent molecules that are characterized by red-tailed broad emission band and short lifetimes, QDs have several attractive optical features that are desirable for long-term, multitarget, and highly sensitive bioapplications. QDs have very large molar extinction coefficients, typically on the order of 0.5-5 × 10 M−1 cm−1. This value is approximately 10-50-fold higher than those of organic dyes [8]. Due to the high molar extinction properties, QDs are attractive as highly sensitive fluorescent agents that can be used for the highly efficient fluorescence labeling of cells and tissues. With regard to the photostability, the photostability of QDs is typically several thousandfold more stable against photobleaching than organic dyes [9]. The unique and excellent photophysical properties of QDs allow the real-time monitoring of biological processes over long periods of time and have potentials for cancer biomarker assays and in vivo imaging where much longer times are needed. Another interesting photophysical properties is related to the longer excited state lifetime (20-50 ns), which is about 1 order of magnitude longer than that of organic dyes. Due to the longer lifetime, the effective separation of QD fluorescence from background fluorescence by a time-gated or time-delayed data acquisition mode is also possible [7,10]. Compared with those of organic dyes, the excitation and emission spectra of QDs are well separated and further improvement of detection sensitivity in imaging tissue biopsies is possible [11]. Finally, the size-dependent fluorescence of QDs provides the imaging and tracking of multiple targets simultaneously with single excitation source. This is of particular importance in cancer detection and diagnosis, since it has been realized that a panel of disease-specific molecular biomarkers can provide more accurate and reliable information with regard to the disease status and progression than any single biomarker [12].