Research Article: Quantum Dots for Molecular Diagnostics of Tumors

Date Published: , 2011

Publisher: A.I. Gordeyev

Author(s): T.A. Zdobnova, E.N. Lebedenko, S.М. Deyev.

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Abstract

Semiconductor quantum dots (QDs) are a new class of fluorophores with unique physical and chemical properties, which allow to appreciably expand the possibilities for the current methods of fluorescent imaging and optical diagnostics. Here we discuss the prospects of QD application for molecular diagnostics of tumors ranging from cancer-specific marker detection on microplates to non-invasive tumor imagingin vivo. We also point out the essential problems that require resolution in order to clinically promote QD, and we indicate innovative approaches to oncology which are implementable using QD.

Partial Text

In recent biomedical studies, much attention has been paid to the search for new methods of noninvasive imaging of the internal structure of biological objects. Instruments with a high spatial resolution have been designed, and, consequently, optical methods for investigation are gaining widespread use. One of the most demonstrable and informative methods among these is the fluorescent diagnostics of pathological foci directly in the organism.

Quantum dots are almost spherical nanocrystals 1–10 nm in diameter, consisting of a small number of atoms (500–10,000) of semiconductor materials of groups II–VI (e.g., CdSe, CdTe, CdS, and ZnSe) or groups III–V (e.g., InP and InAs) of Mendeleev’s periodic table. The term “dot” mainly characterizes the extremely small dimension of these objects; while the adjective “quantum” describes the fact that their behavior and properties are described to a significant extent by quantum mechanics, rather than classical mechanics. The decrease in the particle size of the compound to a value smaller than the exciton Bohr radius (e.g., for spherical СdSe particles this diameter is less than 6 nm) results in that the properties of the compound are determined not as much by their chemical composition as by their particle size. In light of this, semiconductor nanocrystals are characterized by their unique optical characteristics and physicochemical properties that distinguish them favorably from other fluorophores that are conventionally used in biology [7].

It is a common requirement when using QDs as fluorophores for tumor imaging that they bind to various targeting molecules, thus ensuring the selective delivery of QDs to tumor cells and their components. The specificity of labeling is provided by the selection of a target that optimally suits each particular case and the corresponding targeting molecule.

One of the most promising and rapidly developing areas of application of QDs is their usage as fluorescent labels during in vitro study of tumor cells: for imaging tumor cells and for localizing the individual molecules expressed in them. The unique properties of QDs, which make it possible to perform multicolor labeling and long-term observation of fluorescence of objects, allow one to considerably broaden the range of conventional methods that are used in this field. In vitro diagnostics is now the only application of QDs out of all alternatives of the biomedical use of QDs which can be quickly implemented in clinical practice (as opposed to the in vivo use of QDs, which requires long investigations of QD toxicity and further consequences of their introduction into the organism).

During the past five years, considerable progress has been made in the application of QDs as fluorophores in experiments on cells and fixed tissues. Meanwhile, the use of these nanoparticles for imaging in multicellular organisms, especially in such highly organized ones as mammals, is only in the early stages of development.

The unique physicochemical properties of QDs make them extremely attractive fluorophores for the in vivo imaging of living objects. The pioneering studies in this field began quite recently (less than 10 years ago); in fact the search for a design of QD optimal for these purposes is ongoing. In this regard, QDs that are used by different laboratories strongly differ in such parameters as their size, shape, charge, concentration, oxidation-reduction properties, surface coating, and physical stability. A wide range of these parameters, in combination with various experimental conditions (treatment time, selection of the model cell lines and media, using the same concentration units, the presence or absence of a targeting agent) make it considerably more difficult to compare the published data on QD biosafety and to get a broad outline. Despite this fact, in a field of extremely diverse and controversial information, a number of regularities have been revealed [90, 98].

Quantum dots are a relatively new class of compounds with seemingly immense potential for use in various types of tumor diagnostics, from the microplate assay for oncomarker detection to noninvasive in vivo imaging of tumors. The unique physicochemical properties of QDs, easily tunable fluorescence spectra, a high quantum yield (particularly, in the IR region), the possibility of excitation over a wide range of wavelengths and narrow emission fluorescence peaks, large section of two-photon absorption, and resistance to photobleaching, make possible a considerable broadening of the capabilities of modern methods of fluorescence imaging and optical diagnostics. These fluorophores allow one to solve problems that are difficult to overcome using conventional dyes; e.g., simultaneous detection of several markers, long-term real-time observation of molecular processes, and taking images of tumors deep in tissues. However, when performing a number of routine tasks, the problems associated with the colloidal nature of QDs outweigh the advantages provided by their optical properties.

 

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