Quantum dots make the brain shine

There is a technology that allows scientists to target cells and color code them. Quantum dots are tiny, nanometer-sized particles that have unique physical properties that allow them to fluoresce in a rainbow of bright colors. They can also be molecularly functionalized, ie they can chemically attach other molecules and proteins to their surface, which in turn interact in a targeted manner with different cells. This makes them well suited for visualizing and tracking molecular processes within cells, including neurons in the brain and other parts of the nervous system.

What are quantum dots and how do they work?

If you take an atom and inject energy into it, for example by irradiating it with light of a certain wavelength, the electrons surrounding the atomic nucleus are excited and jump to a higher energy level. But they tend to be unstable at this higher level and eventually relax back to their more stable lower level. When they do this, they need to part with the extra energy they have gained. They do this by releasing this energy as light.

Quantum dots work in a similar way. But instead of being a single atom, they are a larger semiconductor particle. They absorb light of certain wavelengths and in return emit light – they fluoresce – in different colors. What makes quantum dots such an interesting nanotechnology, however, are their unique properties. First of all, the color in which they fluoresce does not depend on the material they are made of, but on the size and diameter of the quantum dot.

In addition, quantum dots have a broad absorption spectrum – that is, they can be excited over a relatively large range of light wavelengths. However, they have very narrow emission spectra: the wavelengths of light that each quantum dot sends back are a very narrow range. The wavelength determines the color, so a narrow emission spectrum means that quantum dots can emit light in very specific colors. It is for this reason that they create such a distinct rainbow of non-overlapping colors. A narrow emission spectrum, in turn, allows colors to be multiplexed – you can use different colored quantum dots to selectively bind to and mark different molecules and proteins in a cell. That’s a big advantage.

At the same time, they also slowly fade. This means that the intensity of their colors slowly diminishes over time, unlike other molecular markers that are commonly used in cell biology. Scientists use this property to “track” how molecules move within a cell over time, since the quantum dot tag fluoresces over long periods of time.

They also display a blinking property that enables the identification of individual quantum dots in a sample. This enables single-molecule binding events to be identified and tracked over time, which is very difficult to do with other molecular methods.

How can quantum dots target and mark certain molecules? The core of a quantum dot typically consists of a heavy metal such as cadmium selenium or cadmium telluride, although quantum dots made from other materials have recently become possible. This core is surrounded by a non-reactive intermediate layer, for example a zinc sulfide shell. The optical properties of the quantum dot are all the result of the physics associated with its core. But it’s a bespoke outer coating that allows it to specifically bind and interact with target molecules while ignoring everything else. The outer coating is designed to consist of various bioactive molecules that only bind to molecules of interest that are expressed on – or in – the target cells. It is this chemically functionalized outer coating that provides the binding specificity of the quantum dot. In at least some cell types, quantum dots chemically conjugated with naturally occurring molecules are easily internalized into the cells, do not interfere with normal signaling pathways within the cell, and appear to be non-toxic.

Quantum dots in neuroscience

Similar to other cells, quantum dots can be used in neuroscience to visualize, measure, and track individual molecular events over long periods of time, from seconds to many minutes. However, quantum dots are especially well suited for the cells of the brain and nervous system to conduct experiments and measurements in which there is a constrained and tight cellular anatomy, a common challenge in the super-dense cellular networks that make up the brain. For example in the tiny and molecularly overcrowded space of the synaptic gap – the connection point between two neurons.

A growing body of research and work continues to investigate the use of various types of quantum dots to mark neural cells and to study their cell biology. In some cases, and because the outer coating can be chemically functionalized, some groups are investigating the use of quantum dots as biomarkers for diseases such as Parkinson’s. The aim is to develop new diagnostics that can detect molecular changes at an early stage before symptoms and neurological failures occur. This would allow clinicians to intervene sooner and, hopefully, delay or even halt the progression of the disease.

Other work does not focus on diagnostics or cell biological experiments in a dish, but on the use of this technology for clinical use on humans. For example, recent work with carbon quantum dots explored their potential for treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease by destroying the tangles of amyloid proteins associated with disease progression. Other researchers are investigating the possible future uses of quantum dots for brain imaging.

However, as with any newer technology, despite continued and exciting advances, there are a number of challenges and unanswered questions that need to be addressed. This is especially true when it comes to clinical applications in humans. Any enthusiasm must realistically be tempered. One of the biggest concerns is the chemical makeup of the quantum dots themselves. In particular, quantum dots, which contain a heavy metal nucleus that could cause potential toxicity. Other considerations include the need to fully understand how well quantum dots are removed from the brain and body, and all possible changes in internal cell signaling pathways induced by ingestion of quantum dots. Previous in vivo applications have focused on animal models. No study has yet reached clinical testing in humans.

Still, quantum dots offer a unique opportunity to advance scientists’ understanding of the brain. And maybe someday, maybe even new clinical applications – diagnosing and treating neurological diseases in ways that are not possible today. There is a bright future ahead of us.