Nanoparticles vs. Superbugs

The future is now! Quantum dots are nanoscale machines so small that their physical behaviors are determined by quantum mechanics. What’s more, they can be designed to fight antibiotic-resistant pathogens, or superbugs. In Quantum Dot Therapeutics: A New Class of Radical Therapies, we can read a review of papers on just this topic.

Reviews are peer-reviewed papers that don’t track experiments, but rather, literature. They tend to be great introductions to the field (at least, they assume less background knowledge than the introduction of a regular science paper), and they are a helpful source for identifying – and understanding – important papers on that subject.

So here, we get to use a review paper to introduce the world of quantum biology and its potential for human medicine.

How can we hack cell redox balance?

And why do we want to?

The currency and language of a cell is summed up in its redox chemistry. By exchanging electrons, cells can interact with other cells. They can also set off a cascade of chemical reactions involved in cell metabolism. How can you hack the internal redox system of a cell? Quantum dots are an exciting new method.

Quantum dots are nanoparticles that transfer electrons. They do this by acting as semiconductors, and in response to a stimulus (such as light), they control the motion of electrons within the conduction band.

I don’t know what that means, so to understand what a ‘conduction band’ is, I’ve got to dig a little deeper into band theory. This is a gen chem concept within the field of quantum chemistry.

Nonmetal atoms (those atoms on the right of a periodic table) have valence electrons settled and in stable orbits. That means that any electrons in the conduction band exist at energy levels too far from the valence shell; that is, there’s no electron interaction. In metals, however, electrons move between the valence shell and conduction bands, allowing the metal to conduct electricity.

The transition metals are where things get interesting. There is a gap between valence and conduction electrons (like there was for the nonmetals) – but it is jumpable, so electrons can be transferred (like for the metals). This allows transition metals to act as a semiconductor (it conducts, but only some of the time).

With these semiconductive transition metals, we can build quantum dots that move electrons around within a cell, changing the molecules around them. What, exactly, do they change? That depends on how you build it. A quantum dot can be engineered to alter electrons in specific chemical reactions and biosynthetic pathways, depending on what molecule you want to end up with!

Building the Quantum Dot

Selecting the Hitman, Protecting the Host

Put these transition metals into a particle of nanoscale proportions, and you have a quantum dot – a particle so small it obeys the laws of quantum mechanics rather than Newtonian ones.

So what’s the application to therapeutics and human medicine? If you transfer electrons between common substances – say, oxygen and water – you can end up with Reactive Oxygen Species (ROS). These include superoxides (O₂^–), peroxides (H₂O₂), singlet oxygens (O¹₂), and hydroxyls (OH^–). These substances wreak havoc in a cell, often killing it.

So the trick is this: find a Quantum Dot that will kill the right pathogenic cells, but is harmless to host cells. To do this, we can fiddle with the dot’s:

Reduction potential – how strongly does it move electrons around?
Material – which transition metal should it be made of?
Coatings – can we coat the dot with a material that optimizes function?

Messing with these properties, we can hopefully settle on a quantum dot that kills pathogens (even antibiotic resistant ones) but doesn’t exhibit host toxicity, or accumulate in host cells.

We don’t want a quantum dot that will just end up building up in liver or kidney tissue. We don’t want a material that will leach metal ions into human tissues. We don’t want it to kill pathogens – like the superbug MRSA – but also kill human cells!

This review covers research that suggests that superoxides are the only ROS that selectively kill bacterial pathogens without harming mammalian cell tissue. So we know that superoxides are the way to go, and if a material doesn’t natively react this way, we can sometimes use bandgap engineering on the quantum dot to fine tune its redox potential. Presto! It produces superoxides only, kills selectively, and human cells are unharmed.

The review goes on to cover titanium dioxide (TiO₂), an FDA-approved material (you may see it listed in your favorite sunblock) that, in its normal quantum dot state, will react to produce hydroxyl groups. However, it is theoretically possible to engineer it, manipulating it to produce superoxides instead. In fact, the authors observed superoxide formation when they coated TiO₂ dots with zinc sulfide (ZnS) and exposed them to light. Thus, this is a potentially optimal coating to use when building a superbug-fighting quantum dot.

When it comes to toxicity, size matters. A small enough quantum dot can clear through human tissues fairly easily. But coating can help as well – even large quantum dots exhibit low cytotoxicity when coated with safe materials, like ZnS, in the studies reviewed here. Thus, these are other factors to consider when designing your dot.

To produce novel therapeutics and fight superbugs with quantum dots, researchers are continuing to explore this multi-faceted problem. Dot materials, sizes, and coatings should be chosen wisely. By engineering the reduction potentials of these quantum superconductors, we may end up with nanoparticles as safe, effective, selective killers of the superbug threat we see today.

References

Levy, M., Chowdhury, P. P., & Nagpal, P. (2019). Quantum dot therapeutics: a new class of radical therapies. Journal of Biological Engineering, 13(1), 48.

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