Application of functional quantum dot nanoparticles as fluorescence probes in cell labeling and tumor diagnostic imaging
© Zhao and Zeng; licensee Springer. 2015
Received: 30 January 2015
Accepted: 21 March 2015
Published: 10 April 2015
Quantum dots (QDs) are a class of nanomaterials with good optical properties. Compared with organic dyes, QDs have unique photophysical properties: size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. Possessing versatile surface chemistry and superior optical features, QDs are useful in a variety of in vitro and in vivo applications. When linked with targeting biomolecules, QDs can be used to target cell biomarkers because of high luminescence and stability. So QDs have the potential to become a novel class of fluorescent probes. This review outlines the basic properties of QDs, cell fluorescence labeling, and tumor diagnosis imaging and discusses the future directions of QD-focused bionanotechnology research in the life sciences.
KeywordsNanoparticles Quantum dots Optical properties Biomaterials
Quantum dots (QDs) are a kind of semiconductor fluorescent semiconductors, which have gained attraction in recent years by scientists as a novel fluorescent probe [1-6]. Compared with conventional organic fluorescent probes, QDs have shown great potential to be fluorescent probes and images in biology because of their unique optical properties [7-15]. Alivisatos and Nie employed QDs as fluorescent probes in biological staining and diagnostics that provided a novel study to display QDs as labels for cell and tissue research [16,17]. In recent years, QDs have been widely used in many fields of life sciences as fluorescent markers [18-21]. Herein, we briefly review the basic properties of QDs and the application of functionalized QDs as fluorescent probes in biological systems.
The unique properties of quantum dots
QDs have unique optical and electrical properties due to its quantum effect and size effect. When the size of a particle is of nanometer scale, it will cause quantum confinement effect, size effect, dielectric confinement effect, macroscopic quantum effect, and surface effect. Consequently, QDs exhibit many optical properties different from macroscopic materials, and they have a very broad application prospects in biological fluorescent probes and functional materials. Therefore, QDs will have a meaningful effect on the continued development of life sciences [22-28].
Quantum dots have unique optical properties
Quantum dots have large stokes shift
Quantum dots have strong fluorescence intensity and high stability and strong resistance ability to photobleaching
Quantum dots have long fluorescence lifetime
The fluorescence lifetime of typical organic fluorescent dyes is only a few nanoseconds (ns), which is similar to the decay time of autofluorescence of biological samples. While the fluorescence lifetime of QDs can sustain tens of nanoseconds (20 to 50 ns), which makes the fluorescence of QDs still persist and obtain fluorescence signals without background interference when the majority of the auto-fluorescence background has been attenuated after a few nanoseconds of light excitation [39,40].
Quantum dots have good biocompatibility
The chemically modified QDs are less harmful to organisms with good biocompatibility and low cytotoxicity. And it is easy to achieve QD surface functionalization of specific connection and biological labeling and detection in vivo after a variety of chemical modifications .
Since the surface chemical properties of the same kind of fluorescent nanoparticles of different sizes are very similar, the chemical modification method for particles of one size can also be applied to other sizes of particles, making it easy to obtain a series of fluorescent marking materials of the same surface-modified structure but of different optical properties, which greatly simplifies the biochemical modification process of fluorescent probes . In addition, QDs are of good spatial compatibility, a QD can simultaneously couple two or more biological molecules or ligands, so QDs can be used to prepare multifunctional materials for detection and imaging [43,44]. Because of these unique optical properties, QDs can be used as ideal fluorescent probes . And instead of organic fluorescent dyes, QDs will play an important role in the study in the cellular location, signal transduction, intracellular molecular movement, and migration [46,47].
The applications of quantum dots in cell labeling and imaging
The most promising application of QDs is that they can be used as fluorescent probes in biological systems. QDs made of different materials coupled with biological molecules can replace a lot of fluorescent dye molecules and play a significant role in cell biology research. And the light stability of QD markers makes long-term tracking of biological molecules possible, using the labeling technique [48,49].
In the biomedical field, one of the earliest and most successful applications of QDs is in cell biology research; for example, QDs can be used as cell surface markers and intracellular markers . Cell surface markers are obtained by specifically binding QDs with biomolecules to cell surface by streptavidin-biotin system, and the QDs are indirectly marked on cell surface. Based on the fact that green silanized QDs have the characteristics of high affinity with nuclei, Alivisatos et al. directly marked murine fibroblast cell nuclei using the QDs . Taking advantage of electrostatic interactions, they connected avidin to the surface of red silanized QDs and labeled QDs to the F-actin on cell surface by the specificity of biotin-avidin. So, for the first time, the two-color QDs marked individual cells simultaneously.
The applications of quantum dots in tumor diagnostic
Cervical cancer is one of the most fatal diseases, and researchers are actively developing methods of early diagnosis and treatment. Currently, QDs have been successfully applied to tumor imaging at the cellular level. Rahman et al.  combined overexpression SiHa cervical cancer cells of epidermal growth factor receptor (EGFR) with the monoclonal antibody of biotinylated EGFR and found that the fluorescence intensity of the experimental group was significantly higher than that of the control group after being irradiated by two kinds of excitation light of the confocal fluorescence microscopy. And the tumor cells could be identified from the full organization by the QD probes, which have a more competitive advantage than the traditional contrast agents. It proved that QD probes can detect cervical cancer at the molecular level, which provides a new way for early diagnosis of cervical cancer. The strong fluorescent stability of QDs also shows superiority in research on living animal. In recent years, Ren et al. have reported CdSeTeS QDs modified with alpha-thio-omega-carboxy poly(ethylene glycol) (HS-PEG-COOH), and the modified QDs were linked to anti-epidermal growth factor receptor (EGFR) antibodies . QDs with the EGFR antibodies as labeling probes were successfully applied to targeted imaging for EGFR on the surface of SiHa cervical cancer cells through conjugation of QDs with the anti-EGFR antibodies. These preliminary results indicated that CdSeTeS QDs can become useful probes for in vivo targeted imaging and clinical diagnosis.
With the development of nanotechnology and the improvement of QD marking technology, QDs are increasingly showing its great value and good prospects, especially in the optical and biological aspects, due to their unique physical and chemical properties. Certainly, far more than this, QDs are also a powerful tool for drug screening. QDs will become the most promising fluorescent markers; for example, QDs show great potential for cell imaging, fluorescence immunoassay, etc. Especially, QDs have made great progress in the cellular imaging in recent years, showing far more advantages than the traditional organic dyes. The technology of using QDs as fluorescent markers of living cells is gradually becoming mature, diverse, and practical. It can be predicted that the QD fluorescence technology will open up new horizons for researches in complicated life phenomena of living cells.
This work was supported by the National Natural Science Foundation of China (U1204201), Postdoctoral Science Surface Foundation of China (No. 2012 M511570), and Department of Education Science and Technology Research Key Projects of Henan (13A150063).
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