One of the most exciting forefronts of nanobiotechnology is the use of quantum dots, which are defined as semiconductor nanocrystals with excitons in all three spatial dimensions, as fluorescent dyes in biology and medicine. Initially discovered in 1980 by Alexic Ekimov and Louis E. Brus, the advances of quantum dots synthesis significantly promoted fluorescent imaging for both in vitro and in vivo applications.
Quantum dots have a plethora of advantages when compared to conventional organic dyes, such as high quantum yields, no photobleaching, narrow and symmetrical emission, broad excitation, as well as being able to excite using only single excitation. Many products of quantum dots have been commercialized (such as specific nanoprobes), and their use in various therapeutic approaches looks promising.
The use of quantum dots as labels
Quantum dots were introduced as biological probes in 1998, but while there were a myriad of reports describing its use in biology and medicine after the pioneering articles, it’s evident that the use of these probes is still in its infancy. Protocols and preparation methods are continually being improved to enable the use of quantum dots for a particular application.
Single quantum dots conjugated to biological affinity molecules can be used in many different scenarios. For example, in order to label the breast cancer marker Her2 on the surface of malignant cells, quantum dots conjugated to immunoglobulin G and streptavidin were successfully employed. Furthermore, they were also used coupled with oligonucleotides for in situ hybridization.
Quantum dots are a good way to label live cells, which can be stable for as long as twelve days in culture. They have been used to measure cell motility by imaging of phagokinetic tracks, and it was demonstrated that cells were capable of engulfing nanocrystals as they travel. Cadmium and other heavy elements in their composition enable their use as contrast probes in X-ray and transmission electron microscopy.
Applications for in vivo use of semiconductor quantum dots are imaging of tumor vasculature, imaging of tumor-specific membrane antigens, as well as imaging of sentinel lymph nodes. Multicolor fluorescence imaging of cancer cells can be accomplished by systemic injection of quantum-dot-based multifunctional nanoprobes.
Quantum dots in therapy
A successful use of quantum dots in labeling and detection has encouraged researches to continue with the development of this technology for treatment purposes. In addition to using quantum dots as labels for traceable drug delivery, major area of application is using them as an efficient drug carrier system.
Distinctive surface and structural properties (such as their uniform and tunable size, as well as flexible drug linking) have enabled their usage in targeted drug delivery. Quantum dots have been applied to cell-lines and small research animals as drug carriers, proving to be a superb discovery tool for drug screening and validation.
For example, an antihypertensive drug captopril has been conjugated to the surface of quantum dots to study its pharmacokinetic and pharmacodynamic properties in stroke-prone rats with hypertension. It has been shown that such conjugates can successfully decrease blood pressure, but the problem is with retaining its activity after initial 60 minutes.
Doxorubicin, an anthracycline antibiotic that is widely used in chemotherapy, can be immobilized onto quantum dots in order to improve and control the kinetics of drug release. In addition, quantum dots can act as delivery vehicles for small interfering RNAs, which are powerful tools for silencing gene expression.
The unique features of quantum dots have already cemented their role in the burgeoning fields of nanomedicine and nanobiotechnology. If high-quality quantum dots can be prepared from compounds that are non-toxic (e.g. carbon and silicon), the clinical relevance of these semiconductor nanocrystals could be immense.
Although quantum dots are not designed to assist in every application, the trends are evident that they will become dominant fluorescent reporters in biology and medicine over the next decade. A new class of protean multifunctional nanoparticles (either for diagnostic or the therapeutic use) could emerge from the conjugation of quantum dots with targeting agents and photosensitizers.