Semiconductor Quantum Dots and Rods for In Vivo Imaging and Cancer Phototherapy

The following sections are included:

• Contents
• Preface
• About the Author

Semiconductor quantum dots (QDs) are nanocrystals that are just several nanometers in size, and therefore exhibit marked quantum size effects. Compared with organic dyes and fluorescent proteins, QDs possess interesting optical properties, including broad absorption, sharp size-tunable emission, high quantum yield and strong resistance to photobleaching. Since QDs were used as fluorescent nanoprobes for cell labeling and imaging in 1998, these fluorescent nanomaterials have been widely studied for in vitro and in vivo imaging applications. In vivo imaging using near-infrared (NIR) QDs shows potential for use in cancer diagnosis. Nanoparticles, including QDs, usually quickly accumulate in sentinel lymph nodes (SLNs) by passive targeting after being injected intramuscularly into a body. Therefore, using QD fluorescence for SLN mapping may be a convenient technique compared with other in vivo imaging applications such as tumor target imaging. Importantly, axillary SLNs containing NIR QDs can be imaged directly through deep tissue without surgical management, because the NIR fluorescence of such QDs can penetrate through tissue. In addition, the NIR fluorescence from the QDs in the SLNs can be observed for several hours or even longer. These advantages are benefit for SLN mapping. In this chapter, the optical properties of QDs and their use in animal SLN mapping are described. Future perspectives including the feasibility of clinical translation are also discussed.

In vivo tumor-targeted fluorescent imaging is a particularly promising method for real-time detection of solid tumors located in a body. This is a convenient and inexpensive technique compared with traditional imaging methods such as magnetic resonance and computed tomography imaging. In vivo tumor-targeted fluorescent imaging requires fluorescent agents that exhibit bright stable near-infrared (NIR) fluorescence and high tumor-targeting efficiency. High-quality NIR semiconductor quantum dots (QDs) covalently conjugated with biorecognition molecules like antibodies are excellent candidates as fluorescent agents because of their small size and high fluorescent quantum yield and photostability. In this chapter, in vivo passive and active tumor targeting of QDs, as well as the trajectory of tumor-targeted delivery of a single QD bioconjugate in live mice, are described.

In vivo near-infrared (NIR) fluorescent imaging has several advantages, such as good biological safety (e.g., no radiological hazard), quantitative sensitivity, easy operation, and real-time imaging. However, this noninvasive imaging technique is difficult to use for deep tissue detection because the ability of NIR light to penetrate animal tissues is limited, and animal tissues also usually have strong background autofluorescence. These limitations can be overcome by optical imaging based on bioluminescence resonance energy transfer (BRET). In this chapter, red and NIR semiconductor quantum dot (QD)-BRET systems and their use In vivo imaging in small animals are discussed. In the QD-BRET systems considered here, red or NIR QDs are conjugated with an eightmutation variant of Rotylenchulus reniformis luciferase (Luc8). When the QD-Luc8 bioconjugates encounter the substrate coelenterazine, Luc8 emits blue luminescence and this light energy is transferred from Luc8 to the QDs. This allows the QDs to emit red or NIR fluorescence without external excitation. This bioluminescence imaging technique can be used for deep tissue detection without interference from tissue autofluorescence, which is interesting to both materials and biomedical scientists.

Semiconductor nanocrystals include zero-dimensional spherical quantum dots (QDs) and one-dimensional semiconductor quantum rods (QRs) and quantum wires (QWs). Both QDs and QRs have received extensive attention in biomedical research because of their interesting optical properties, including bright and stable size-dependent fluorescence and other unique optical properties such as narrow symmetric fluorescent emission spectra. However, the optical properties of QRs make them better fluorescent probes for in vitro and in vivo biomedical imaging than QDs. For example, QRs have brighter fluorescence with slower photobleaching than QDs. Therefore, QRs are suitable for long-term fluorescence imaging. In addition, QRs have a larger surface area than QDs for conjugating biomolecules, which allows QR bioconjugates to exhibit stronger functions than QD ones. In this chapter, the optical properties, cell labeling and imaging applications, and ability to penetrate physiological barriers of QRs are described. The use of QR-bioluminescence resonance energy transfer (BRET) systems using QRs as energy acceptors and the toxicity of QRs are also discussed.

Photodynamic therapy (PDT) using photosensitizers is an adjuvant treatment with a long history in clinical practice. Photosensitizers with excellent properties are required to improve the efficacy of PDT. Because most solid tumors grow in deep tissue, the absorption spectra of photosensitizers need to appear in the near-infrared (NIR) region. The optical properties of semiconductor quantum dots (QDs) depend directly on their size. The absorption spectrum of QDs can be shifted to the red or NIR region by increasing their size. Therefore, QDs may be a good choice for deep-tissue PDT. In addition, upon red or NIR laser irradiation, QDs not only efficiently generate reactive oxygen species (ROS), e.g., singlet oxygen, but also release toxic ions, especially heavy metal cations. Both ROS and heavy metal ions can damage DNA and induce cell apoptosis. In this chapter, the mechanism of QDs in PDT, the PDT behaviors of QDs including those of QDs used directly for cancer PDT, fluorescence resonance energy transfers (FRET)-based PDT and bioluminescence resonance energy transfer (BRET)-based PDT are discussed. The future prospects of QDs in PDT are also considered.

Semiconductor quantum dots (QDs) are novel powerful fluorescent nanoprobes that can be used for in vitro and in vivo biomedical labeling and imaging. QDs have attracted considerable attention from biomedical researchers during the past decade because they exhibit several unique optical properties compared with conventional fluorescent dyes. Recently, researchers found that QDs can also kill cancer cells through their photothermal effect. QDs with deep colors, such as brown or close to black, are more suitable for in vivo cancer photothermal therapy (PTT) than those with light colors like yellow and red. This is because deeply colored QDs strongly absorb in the red and near-infrared (NIR) region. NIR light can penetrate deep into animal tissues, and deeply colored QDs can efficiently convert NIR light into heat energy, which can damage cells. PTT is a new direction of research for QDs. In this chapter, the use of cadmium- and copper-based QDs, for cancer PTT is discussed. The advantages and disadvantages of these QDs in PTT as well as their future prospects in this field are considered.

Developing nanomaterials with multiple functions and low toxicity is currently one of the research goals in nanobiomedicine. Hybrid nanocomposites composed of semiconductor quantum dots (QDs) and graphene nanosheets are novel multifunctional nanomaterials that can be used for cancer fluorescence imaging, and photothermal and photodynamic cancer therapy. Graphene oxide (GO) and reduced graphene oxide (rGO) are the most popular types of graphene nanosheets used in biomedical research. Toxic metal cations, like cadmium ions, and drugs, such as doxorubicin, may be strongly adsorbed by GO and rGO. Therefore, the toxicity of QDs is lowered by combination with graphene nanosheets because the toxic metal ions released from the QDs are captured by the nanosheets. In addition, a large amount of drugs can be loaded onto QD-GO/rGO nanocomposites. Such drug-loaded QD-GO/rGO nanocomposites may exhibit the synergistic effects of drug therapy (e.g., chemotherapy), and photothermal and photodynamic therapies. In this Chapter, the advantages of combining QDs with graphene nanosheets, bioimaging and cancer therapy using QD-GO/rGO nanocomposites and their preparation are discussed. The disadvantages of QD-GO/rGO nanocomposites such as low fluorescence quantum yield are also described.

Semiconductor quantum dots (QDs) and magnetic materials both play very important roles in biomedicine. The development of nanocomposites that synchronously possess bright fluorescence and strong magnetism has attracted great attention because such materials can be used for bioseparation and multimodal cancer imaging and therapy. For instance, magnetic-fluorescent nanocomposites have been fabricated that can separate cancer cells and allow fluorescent identification, be used for both magnetic resonance and fluorescence imaging, and effectively kill cancer cells through synergistic photothermal and photodynamic effects. The methods of combining QDs and magnetic nanoparticles include seed-mediated growth, paramagnetic metal ion-doping, conjugating QDs onto magnetic nanoparticles using cross-linking agents and incorporating QDs and magnetic nanoparticles into spheres, etc. In this Chapter, the preparation methods and biomedical applications of QD-magnetic nanoparticle hybrid nanocomposites are discussed. The limitations of these nanocomposites are also considered.