Quantum dots are defined as the nanometer size semiconductor particles that are made up of II -VI or III-V groups of elements. They are also called as semiconductor nano-crystals (Michalet, Pinaud et al. 2005). They are the minute particles that are of 100nm in size. They are widely used in different fields to know the physical aspect, fluorescence imaging, quantitative, detection and targeting of the objects(Smith, Dave et al. 2006). As they have dense structure and small size they exhibit different physical and chemical properties. They have optical and electronic properties based on the "quantum confinement effect". Due to QDs size and configuration they exhibit a wide range of light spectrum from visible region to infrared region with diverse wavelengths. Usually they are layered as semiconductor as the core and covered by shell (Murray, Norris et al. 1993). QDs have special properties like brightness, photostable fluorophores with wide excitation spectrum but with an exception of small emission that is under the control of size and core configuration (Bruchez, Moronne et al. 1998). They have different uses such as biomedical imaging, multiplex coding, single cell microscopy, fluorescence resonance energy transfer analysis, pathogen and toxin detection etc.
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Due to the new developments around the world biological imaging has become very significant. With the help of imaging various subcellular constituents, in vivo mechanisms, structure, function can be observed. It enables to view the objects in 2D or 3D configurations (Vonesch, Aguet et al. 2006). The in vivo or in vitro imaging such as tumor specific receptors, malignant tumor, immune response tumor etc is viewed with the help of QDs (Robe, Pic et al. 2008; Sen, T. J. Deerinck et al. 2008). In in vitro and in vivo imaging the usual problem faced is the aqueous solubility of QDs. In order to overcome this problem an alternative method such as exchanging ligand and by coating of plymer can be used. With respect to the in vivo the major issue is the toxicity, by protecting ligand it can be resolved (Selvan 2010). Commonly used probes for bioimaging are Si QDs for both in vivo and in vitro. It is used because it has the capacity to break to silicic acid that can be eliminated through urine (Gao and Nie 2003; Selvan 2010).
Traceable drug delivery helps in the examination of the pharmacokinetics and pharmacodynamics of the drugs. QDs are recently used in cells and on tiny animals because of in vivo toxicity and degradation. Traceable therapeutics have significant role in drug detection, confirmation and releasing. For the delivery of the drugs the QDs initial range can be adjusted between 2-10nm and later changes to 5-20nm subsequent to polymer encapsulation. The QDs combination helps to find out the drugs magnitude, effectiveness, peculiarity and dimensions which is mainly required for drug delivery (Choi, Liu et al. 2007). The QDs deliver drugs particularly at subcellular range. In contrast to the organic dyes QDs are merged with ligands at particular place that are photostable and clear. QDs reduce the adverse implications of the drugs (Ghaderi, Ramesh et al. 2011).
Role of Quantum Dots:
Quantum Dots have several useful applications in the field of life science. The important property of QDs such as high intensity and photostability has helped enormously in the imaging and marking fields. Due to the harmless and biocompatible property it is useful to in vivo imaging and targeting. They are used in detecting experiments because of their sturdiness. QDs easy and usual production has enabled quantitative and several analyses of biomolecules in vivo. Their application is explained below (Walling, Novak et al. 2009 ).
In vivo imaging:
The QDs optical properties are useful as in vivo labeling. There is addition of several targeting probes to a particular label of definite binding site due to the QDs size and surface area. The main drawback of QDs is the big size (approximately 4-20nm) that it is difficult to pass through the vascular endothelium and cannot be excreted through the urine. The site where QDs probes are addressed may be restricted to vascular contact like the endothelial receptors. Phagocytic cells consume the nanoparticles into the organs such as spleen and liver which are endothelial cells unintentionally. These can be avoided by covering the nanoparticles by polymers which are hydrophilic for example polyethylene glycol (PEG) (Akerman, Chan et al. 2002; Ballou, Lagerholm et al. 2004). By doing this the vascular movement time can be increased. Quantum Dots were injected intravenously to the particular site in the mice.
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The quantum dots (CdSe or ZnS) used were either green or red to particular organs such as tumor blood vessels, lung blood vessels etc. There were non-specific uptakes by the reticulo endothelial tissues seen in mice (Akerman, Chan et al. 2002). It was not harmful when the actual part of the body is attached to endothelial structure for example lymph node. There was usage of near- infrared light as imaging system, where quantum dots like CdTe/CdSe were applied (Peymani, Afifi et al. 2007). This has given a new way to produce quantum dots with high efficiency of emitting light (Bailey and Nie 2003). The quantum dots excised were pahgocytosed by the dentritic cells which travelled to the lymph nodes. This was the advantage method as there was not necessary for cutting the animal's skin rather could be visualized directly which was major success in the field of radioactivity, which is used recently. Inner parts of the body are seen clearly with the help of QDs which helps the surgeon to operate (Ghasemi, Peymani et al. 2009). It is useful to locate the tumor cells and treat them particularly. With the help of imaging process the errors were reduced and proved that the excision of the lymph node completely where it avoids trauma. This method is not adapted in humans (Gao and Nie 2001; Akerman, Chan et al. 2002; Ballou, Lagerholm et al. 2004). The QDs taken into the body is thrown out of the body as waste material before it undergoes degradation process.
The QDs properties such as cytotoxicity are used in cultured liver cells (Derfus, Chan et al. 2004). To avoid oxidation the outer area of QDs are layered suitably where the toxic and carcinogenic cadmium ions are discharge.
Traceable drug delivery:
Traceable drug delivery is used by living organisms which are important in the field of biology for the drug detection, confirmation and liberation properties (Gao and Nie 2001). It is carried out for the reason as the living organisms such as small animals, cells are used for trial basis. In comparison optical imaging are better than the techniques like MRI (magnetic resonance imaging), PET (positron emission tomography), as it is perceptive, quantitative and not much expensive where it can reduce the novel drug expansion significantly. Hence QDs are used for the drug delivery because of its size and features. In the upcoming field the QDs production will permit to enter deep into the tissues for drug carriers which are very useful.
QDs help the hydrophobic, minute drugs to enter into the inorganic nucleus and amphiphilic polymer. For example siRNA and antisense ODN (oligonucleotide) uses QDs for the drug delivery. They have the capacity to locate, penetrate deep into the tissues and may cure the disease (Choi, Liu et al. 2007).
The most important technique is the RNA interference (RNAi) used for the inhibition of the genes and helps in study of the therapeutics. There is use of liposomes, silica, gold nanoparticles used for the delivery of drugs (Bielinska, Chen et al. 1999; Chesnoy and Huang 2000; Takeshita, Minakuchi et al. 2005). Under the in vivo circumstances the drug release capability is low. In siRNA there is no definite intrinsic signal for long term and the imaging process is difficult.
QDs are merged with amphipol for the delivery of siRNA. They are polymers with hydrophilic and hydrophobic chains. They have the property of releasing proteins into the cell bilayer by dissolving them (Tribet, Audebert et al. 1996; Nagy, Kuhn Hoffmann et al. 2001; Gorzelle, Hoffman et al. 2002). In comparison amphinol has the capacity to bind to the transmembrane of the proteins and helps in the delivery of the drug without dislocating the cell membrane.
Exterior hydrophobic ligand nanoparticles that are layered are combined with amphipols which are used for the releasing of the siRNA particles. By doing this it is useful to deliver into the cytoplasm without damaging the enzyme degradation. This combination helps in both in culture media and serum free media. It decreases the toxicity level also. For the siRNA imaging the QDs help in supplying the intense and constant fluorescent indication (Gao).
The application of nanoparticles for the multi-parameter comprehensive study of physiological and pathological processes in biomedical research as well as for advanced diagnostics and therapy in clinical practice presents a surging trend in nanomedicine. QDs, in particular, have emerged as one of the most promising classes of nanoparticles for biomedical imaging, drug delivery, and sensing due to their unique photo-physical properties and versatile surface chemistry. Biofunctionalization of inorganic QD cores facilitates interaction of nanoparticles with biological systems and enables direct participation in biological processes. As a result, QD probes have been utilized in a wide variety of applications spanning in vitro molecular pathology, live cell imaging, and in vivo drug delivery and tracing. With each application QDs have opened new horizons of multiplexed quantitative detection, sensitive high-resolution fluorescence imaging, and long-term real-time monitoring of probe dynamics. Aiming at expanding QD functionality even further, early steps have been made towards engineering of QD-based multi-functional nanodevices that promise to combine the benefits of multiple imaging modalities and incorporate the imaging, drug loading, and sensing capacities within a single nanoparticle. Yet, currently available QD probes are far from being ideal, leaving plenty of room for improvement of existing and development of novel nanoparticle designs. In this review we have discussed the future directions of QD-based bio-nanotechnology research and outlined the major design principles and criteria, from general ones to application-specific, governing the engineering of novel QD probes satisfying increasing demands and requirements of nanomedicine.
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