Quantum Dots in Biological Research

Quantum dots are semiconductors produced as nano-sized crystals. They are composed mainly of the heavy metals cadmium and selenium and are only 4 to 12 nm in diameter. They have the unique property of size-dependent emission spectra that can be excited at a single wavelength. This facilitates multi-colored imaging to illustrate different components on a single scan, as targeted quantum dots each emitting a different color can be introduced. The fluorescence they emit is extremely bright and can be seen by eye through a fluorescent microscope. Furthermore, quantum dots are stable and continue to fluoresce intermittently allowing processes to be viewed over extended timescales.

These unique optical properties have made quantum dots a valuable tool in a wide range of interesting and important applications.

Biological applications

Probes for studying biological systems need to be dispersible in aqueous solution over a wide range of pH and ionic strengths, which limits the use of organic dyes. Quantum dots provided the perfect solution, being nano-sized and chemically inert. Furthermore, their tiny size means that quantum dots can access the smallest of spaces and attach to small molecules without interfering with their function. Consequently, since quantum dots were first used in biological research in 1998, there has been an explosion in their use and in the range of potential applications.

Quantum dots can be directed to specific targets by attaching them to antibodies, peptides, or small molecules. The fluorescence can then be tracked providing a valuable tool for research, disease diagnosis and targeted therapy.

Quantum dots have been used in cell-labeling studies, biosensing (e.g., immunoassay), in vivo imaging studies (to view native processes in living animals) and numerous diagnostic applications (including cancer management, blood flow investigation, virus detection)(1). It has also been proposed that quantum dots could be used to deliver targeted therapy to treat tumors.

Toxicity

Unfortunately, the quantum dot story is not all good news. Their high heavy metal content makes them extremely toxic to living creatures. Heavy metals cause developmental abnormalities and serious health issues, primarily affecting the liver and kidneys. They cross the blood-brain barrier, accumulate in adipose tissue, and can remain in the body for up to 10 years.  Long exposure to heavy metals can also lead to carcinogenic effects. In addition, the excitation process (which causes the fluorescence) results in the release of destructive reactive and free radical species.

This cytotoxicity remains a barrier to the use of quantum dots in vivo, but steps have been taken to minimize the toxicity by modifying the quantum dots with proteins or DNA or adding a protective coating. One such technique is maltodextrin capping of quantum dots(2), which has been reported to control toxicity related to cadmium and selenium leakage and proposed as a viable option to extend in vivo applications.

Clear and Stained Chicken Embryo - Image Credit: Image ID: 103824863, Copyright: Pedro Bernardo via Shutterstock.com

Clear and Stained Chicken Embryo - Image Credit: Image ID: 103824863, Copyright: Pedro Bernardo via Shutterstock.com

The extent of the toxicity of maltodextrin-modified quantum dots has recently been studied in chicken embryos to assess how effective the coatings are in containing the toxicity(3). Chicken embryos are readily available and provide an easy-to-use model for toxicity testing. Addition of maltodextrin-modified quantum dots to chicken embryos was found to cause dose-dependent. Low concentrations of the maltodextrin quantum dots increased the rate of cell growth but did not cause any apparent toxicity. However, higher concentrations of the maltodextrin-'protected' quantum dots, were found to be cytotoxic and embryotoxic. The most marked toxicities were in the heart, central nervous system, neural tube and somites (distinct areas of the embryo that will later develop into specific body parts).

It was also reported that the chorio-allantoic membrane of the chicken embryo, which is highly vascularized, was successfully visualized using quantum dots. The quantum dots circulated unchanged in the embryonic blood vessels for 4 days. This could provide a model for studying the growth of blood vessels, which is an important aspect in the control of many cancers.

Although, there is much potential for quantum dots in biology, further research to develop an effect means of managing the associated toxicity is needed before they can be used in vivo.

Acknowledgement

This work was carried out using the In-Vivo Xtreme from Bruker. For more information, please visit: https://www.bruker.com/products/preclinical-imaging/opticalx-ray-imaging/in-vivo-xtreme/overview.html

References

  1. Rosenthal SJ, et al. Biocompatible Quantum Dots for Biological Applications Chem Biol. 2011 January 28; 18(1): 10–24
  2. Rodríguez-Fragoso P, et al.  Synthesis, characterization and toxicological evaluation of maltodextrin capped cadmium sulfide nanoparticles in human cell lines and chicken embryos. Journal of Nanobiotechnology 2012;10:47.
  3. Medintz IL. et al. Potential clinical applications of quantum dots. Int J Nanomedicine. 2008 Jun; 3(2): 151–167.

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Last updated: Mar 6, 2019 at 4:59 AM

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