Quantum Dots in Cancer Imaging and Treatment 521 Active and Passive Targeting for QDs

Having superior light-emitting properties, QDs are excellent candidates for tumor imaging if they can be effectively delivered to tumor sites. Both passive and active targeting mechanisms are being aggressively pursued in order to achieve this goal. Numerous studies have reported methods to lengthen circulation time of QDs in the blood and target QDs to cancerous tissues (Gao et al. 2004a; Âkerman et al. 2002; Rosenthal et al. 2002). Coating QDs with polymers (such as PEG) to avoid uptake by the RES, thereby improving circulation time, is an attractive approach being actively studied. For example, PEG-coated CdSe-ZnS (core-shell) QDs have been shown to circulate longer in the mouse blood stream (half-life more than 3 h) compared to small organic dyes, which are eliminated from circulation within minutes after injection (Ballou et al. 2004). These PEG-coated QDs were also demonstrated to fluorescence after at least 4 months in vivo. It is believed that these PEG-coated QDs are in an intermediate size range in which they are small and hydrophilic enough to slow down opsonization (that is, the alteration of a particle's surface either by the attachment of complement proteins or antibodies specific for the antigen, so that the particle can be ingested (phagocytosed) by phagocytes, macrophages, and/or neutrophils) and reticuloendothelial uptake, but they are large enough to avoid renal filtration.

Taking this a step further, some researchers have conjugated PEG-coated QDs with ligands that can recognize cell membrane receptors (such as HER2, disialo-ganglioside (GD2)) that are overexpressed on cancer cells. This approach is being pursued both for active and passive targeting to achieve the goal of maximizing accumulation of QDs at tumor sites. For example, a new class of QD conjugates containing an amphiphilic triblock copolymer for in vivo protection, targeting ligands for tumor antigen recognition, and multiple PEG molecules for improved biocompatibility and circulation has been developed (Gao et al. 2004a). In this study, CdSe-ZnS (Core-Shell) QDs encapsulated in a copolymer layer, tri-n-octylphos-phine oxide (TOPO), coated with PEG and conjugated to a prostate-specific membrane antigen monoclonal antibody (PSMA) were prepared. PSMA has previously been identified as a cell surface marker for both prostate epithelial cells and neo-vascular endothelial cells (Chang et al. 2001) and has been selected as an attractive target for both imaging and therapeutic intervention of prostate cancer. These QD conjugates have been targeted to tumor sites in mice through both active and passive targeting mechanisms and have enhanced fluorescent imaging ability.

5.2.2 QDs in Drug Delivery and Therapy for Cancers

In addition to utilizing QDs in imaging, there is a growing interest in using QDs for drug delivery and therapy. Firm control over the size of QDs during nanocrystal synthesis will allow for the evaluation of the nanoscale size effect on the delivery efficiency and specificity, and therefore, identification of the optimal dimensions of drug carriers. High surface-to-volume ratios of QDs allow scientists to impart multiple functionalities on single QDs to develop a multifunctional vehicle while keeping the overall size within the optimal range. For example, by coating a QD with an amphiphilic polymer layer (such as poly(maleic anhydride-alt-1-octadecene) (PMAO), octylamine-modified poly(acrylic acid), etc.), hydrophilic therapeutic agents and targeting biomolecules (such as antibodies, peptides, and aptamers) can be immobilized onto the hydrophilic side of the amphiphilic polymer and small molecular hydrophobic drugs can be embedded between the inorganic core and the amphiphilic polymer coating layer as illustrated in Fig. 7a. Figure 7b shows an image of fixed breast cancer SK-BR-3 cells incubated with a monoclonal anti-Her2 antibody (which was used to bind to the external domain of Her2) and a goat anti-mouse IgG conjugated to QDs with an emission maximum at 630 nm (QD 630-IgG). Her2 was clearly labeled with QD 630-IgG (the outer "ring" in the picture).

Fig. 7 (a) Schematic of QDs fabricated to carry drugs and a targeting ligand and (b) fixed breast cancer SK-BR-3 cells incubated with a monoclonal anti-Her2 antibody and a goat anti-mouse IgG conjugated to QDs with an emission maximum at 630 nm (QD 630-IgG). Her2 was clearly labeled with QD 630-IgG (shown in the outer ring). The nuclei were counterstained with Hoechst 33342 (the inside region). Scale bar represents 10 mm (Adapted with permission from (Wu et al. 2002))

Fig. 7 (a) Schematic of QDs fabricated to carry drugs and a targeting ligand and (b) fixed breast cancer SK-BR-3 cells incubated with a monoclonal anti-Her2 antibody and a goat anti-mouse IgG conjugated to QDs with an emission maximum at 630 nm (QD 630-IgG). Her2 was clearly labeled with QD 630-IgG (shown in the outer ring). The nuclei were counterstained with Hoechst 33342 (the inside region). Scale bar represents 10 mm (Adapted with permission from (Wu et al. 2002))

This integrated nanoparticle may serve as a magic bullet that will not only identify, bind to, and destroy tumor cells but will also emit detectable signals for real-time monitoring of its trajectory.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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