Developments in the Future of Cancer Treatment with Photodynamic Therapy

Posted on January 27, 2019 by | Leave a comment

Cancer has long been a devastating condition and one that is difficult to treat, thanks to its ability to quickly propagate throughout the body. As well, the fact that cancer is contained within the body poses the issue of how to kill it off, as toxins will kill both cancer cells and normal cells. This is a problem that researchers are trying to solve by investigating a treatment named Photodynamic Therapy.

Photodynamic Therapy involves the injection of a compound called a “photosensitizer” into the bloodstream. A photosensitizer is a compound that is activated by exposure to light, and in this case produces toxic chemicals once activated. The photosensitizer is allowed to cycle throughout the bloodstream for 1-3 days, at which point it will only remain in cancer cells and not normal cells. A fiber optic cable can then be inserted into the body in order to reach the area with the tumor so that the photosensitizer can be activated.

An example of fiber optic cables used in surgery. Source: Max Pixel

However, new research from Columbia University may present an easier way of approaching Photodynamic Therapy, one that does not require invasive procedures. The team of B. D. Ravetz et al. have discovered a method for activating photosensitizers from outside the body. They do this by using two compounds, one to absorb near-infrared (NIR) light and transfer that energy to the other, which then emits higher energy light.

A diagram showing IR compared to visible light. Source: Wikimedia Commons

The fact that NIR light can be used for this presents some interesting applications. Unlike visible light, NIR is able to penetrate human skin and flesh quite far, meaning photosensitizers can be activated from outside the body, no incisions required! Another advantage of this is that NIR light is lower in energy than visible, meaning it has a very low risk of damaging surrounding cells.

Now, how does this low energy NIR light become high energy visible light? This is done by utilizing a process called Triplet Fusion Upconversion. This same process is actually used in modern solar cells! The “sensitizer” is first excited by the NIR light, and soon loses energy from being excited and transfers it to the “annihilator.” If two energized annihilators interact, it generates a single more energized form through “triplet fusion.” This final high energy form is what then emits the visible light. Here is a brief animation that shows a similar upconversion process.

A diagram showing upconversion processes. “Emitter” is the same as Annihilator. Source: Wikimedia Commons

While this development is very promising, more testing has to be done before this can be used on humans. The toxic chemicals produced by the photosensitizer still hold a risk of killing normal cells, so tests will have to be able to control the production of these toxins. As well, the toxicity of the sensitizer and annihilator molecules will need to be evaluated too. Hopefully this procedure can be perfected in the near future, so that a safe and effective method for killing cancer can become widespread.

– Nicholas Patterson

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Ocean Acidification: Say Good-Bye to the Oceans We Once Knew

Posted on January 27, 2019 by | Leave a comment

Freak snowstorms in Africa, unusually hot winters, and more natural disasters. Events like these are becoming more frequent occurrences than ever before, and so are the words to explain them, Climate Change.

Although natural disasters on land may get more attention, one of the largest concerns should be is what happens in the ocean. Ocean acidification, due to the increased levels of carbon dioxide in our atmosphere, has one of the most significant impacts. Our ocean is a carbon dioxide sink, as it absorbs over 25% of the carbon dioxide that we emit into the atmosphere.

Due to the ocean dissolving more carbon dioxide, carbonic acid concentrations have also increased, resulting in lowering of the pH. Dr. Trional McGrath is a Chemical oceanographer from the National University of Ireland and she predicts that ocean acidification will increase by 170% by 2100!

Figure 1: The chemical process of Ocean Acidification by increasing carbon dioxide emissions. Source: CeNCOOS

Now, why do we care? We don’t live in the ocean so why would it effect us?

Carbonate ions are essential building blocks for marine life when forming shells. Figure 1 shows that as the H+ concentration increases, more of the carbonate ions are going to be tied up as carbonic acid. This results in less material for marine life to make their shells and other structures from.

Figure 2: A Sea Butterfly (i.e. Limacina helicina). An important food source in the ocean. Source: Mashable

 

A study was done where they placed Sea Butterflies in an ocean environment with the pH that is predicted for 2100. Their shells were essentially dissolved in as little as 45 days! Figure 3 below shows this process over that timeline. Even if only a few species are really effected by the pH change, this could have detrimental impacts all the way up the food chain, eventually effecting human’s supply of food!

Figure 3: The Sea Butterflies shell dissolving over 45 days in the predicted pH of the ocean in 2100. Source: TED

This is only one example of the dramatic effect that ocean acidification can cause, but everything from coral to predators of the sea are at risk. If we don’t do something to help reduce the current rate of carbon dioxide being dissolved into our ocean, then in the not too distant future, we won’t be able to recognize the oceans we once knew.

~ Amanda Fogh

“The excess carbon dioxide in the atmosphere that is turning the oceans increasingly acid – is a slow but accelerating impact with consequences that will greatly overshadow all the oil spills put together. The warming trend that is CO2-related will overshadow all the oil spills that have ever occurred put together.” ~ Sylvia Earle (Marine Biologist and Explorer)

 

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The Antibiotic Resistance Crisis

Posted on January 24, 2019 by | 1 comment

 

“Antimicrobial Resistance – Mutation.” National Institute of Allergy and Infectious Diseases, Feb. 2009, www.niaid.nih.gov/topics/antimicrobialResistance/Understanding/Pages/mutation.aspx.

The development of antibiotic-resistant bacteria is a growing concern that is quickly sweeping up the attention of medicinal chemists and doctors. The growing use of antibiotics as the standard for treatment has led to the increase of drug-resistant bacteria; commonly known as “superbugs.” As the drug is repeatedly introduced to the bacteria, eventually mutations will arise in future generations of bacterium¹ that will allow it to be antibiotic-resistant and allow it to multiply and thrive. This increased number of antibiotic-resistant bacteria has led to an increase in sick patients² with bacterial infections that are antibiotic-resistant. As before due to the trivial nature of the infection simple antibiotics would cure the infection, but as per the nature of these “superbugs”, common treatments won’t work anymore, and new drugs or different treatments must be used to cure the infection.

“Causes of Antibiotic Resistance .” World Health Organization, Nov. 2015, www.who.int/drugresistance.

There are many causes to the antibiotic crisis, but one of the more prevalent causes are the over-prescribing of antibiotics and the over-use of antibiotics in livestock and fish farming. Currently, more than 50% of the antibiotics produced are going directly to the feeds of livestock³to keep them from getting sick due to their poor living conditions. By introducing bacteria to a consistent and high volume of antibiotics, eventually, the bacteria will go through mutations in future generations that will allow it to survive these antibiotics and ultimately result in the discontinued effectiveness of that drug. The same concept applies to the over-prescribing of antibiotics, by always introducing the bacteria to the drug eventually it will not be practical to use anymore4. At that point, different drugs would need to be used until they eventually stop working and so on until we reach a point where there would be no more antibiotics left to use to fight these infections.

What causes antibiotic resistance? – Kevin Wu. https://www.youtube.com/watch?v=znnp-Ivj2ek (accessed Feb 16, 2019).

Potential solutions to combat the problem involve something as trivial as proper hygiene. As making sure to wash your hands often, the chance for infection will go down and as a direct result will cut down on antibiotic use. A more futureproof method would be the development of new antibiotics5 or potential re-use of old antibiotics6 that could be re-purposed to combat the problem. No matter the method used to combat this problem or a combination of every method available, this a problem that needs to be addressed as soon as possible, or we are looking at a world where trivial infections can run rampant with no good method of treatment.

~ Danial Yazdan

References:

¹Blair, Jessica M. A., et al. “Molecular Mechanisms of Antibiotic Resistance.” Nature Reviews Microbiology, vol. 13, no. 1, 2014, pp. 42–51., doi:10.1038/nrmicro3380.

²Duin, David Van, and David L. Paterson. “Multidrug-Resistant Bacteria in the Community.” Infectious Disease Clinics of North America, vol. 30, no. 2, June 2016, pp. 377–390., doi:10.1016/j.idc.2016.02.004.

³Bush, Karen, et al. “Tackling Antibiotic Resistance.” Nature Reviews Microbiology, vol. 9, 2 Nov. 2011, pp. 894–896., doi:10.1038/nrmicro2693.

4Chellat, Mathieu F., et al. “ChemInform Abstract: Targeting Antibiotic Resistance.” ChemInform, vol. 47, no. 29, 22 Mar. 2016, pp. 6600–6626., doi:10.1002/chin.201629282.

5Nathan, Carl, and Otto Cars. “Antibiotic Resistance — Problems, Progress, and Prospects.” New England Journal of Medicine, vol. 371, no. 19, 2014, pp. 1761–1763., doi:10.1056/nejmp1408040.

6Frieri, Marianne, et al. “Antibiotic Resistance.” Journal of Infection and Public Health, vol. 10, no. 4, 2017, pp. 369–378., doi:10.1016/j.jiph.2016.08.007.

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Repurposing electron microscopy as a tool for organic chemists

Posted on January 23, 2019 by | Leave a comment

Many small molecules are crucial to life—not only are they used for life-saving drugs, but they also regulate important biological processes within our bodies. In order to understand these small molecules better, scientists have developed various methods to probe what atoms they are made up of, and how these atoms are connected.

Yet one of the newest and most promising of these methods is not so new at all—in fact, it has been a mainstream tool in the field of structural biology for years.

The imaging resolution of biological molecules before and after cyro-EM. Source: Martin Högbom/The Royal Swedish Academy of Sciences.

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Not so green cars

Not so green electric cars

Nowadays with the rise of renewable energy and improvements in rechargeable batteries, buying an electric cars over a traditional gasoline car is becoming cheaper and cheaper. With greenhouse gas (GHG) emissions reaching new highs every year, an electric car is also becoming the more responsible choice.

The four major renewable energy sources in Canada from 2006 to 2016 in megawatts (MW). Source: Natural Resources Canada

However, though an electric car’s engine does not produce any carbon dioxide gas compared to conventional gasoline engines, many consumers often forget the hidden GHG emissions cost from when a car is manufactured.

Sale of plug-in hybrid electric vehicles (PHEVs) and battery electric vehicles (BEVs) in China by year between January 2011 and December 2018 | Source: Mario Roberto Durán Ortiz

In fact, from the moment a car comes out of a manufacturing plant, it would have produced as much as 35 tons of CO2 into the atmosphere. Compared to an average gasoline-powered car that produces 4.6 metric tons of CO2 annually, that is more than seven years of emissions from the plant to the dealer.

In addition, not all electric vehicles are made equal. A plug-in hybrid vehicle (PHEV) still has an internal combustion engine; however, it will use battery power for a certain distance before it switches to gasoline as the fuel source. This combines the strength of both gasoline and battery power since there are no emissions for short trips such as commuting to work but also has the flexibility of being able to quickly refill at a gas station. Battery electric vehicles (BEV) or all-electric vehicle is, as the name suggests, run purely on battery power. These vehicles usually have lower maintenance costs due to lacking the moving parts in the internal combustion engine but initial investment and possible replacement battery in future repairs can be quite costly.

Therefore, even if one were to buy an electric vehicle whose fuel solely comes from renewable energy, it would still leave an initial carbon footprint equivalent to sevens years of GHG emissions.

This discrepancy between what we perceive as beneficial for the environment versus what would practically reduce one’s emissions leaves something to be desired. After all, if buying electric vehicles barely changes one’s total GHG emissions, what would be a better way to save the planet?

Cover of the game “reduce reuse recycle” by Nadine3103

Turns out, it all comes back to the principle of reduce, reuse and recycle. In the modern age, every product that uses plastic and rare metals in some way have to refined or synthesized; this means usually in a plant or mine that most likely emits tonnes of GHG. By using old phones longer, supporting local businesses and buying in season products, emissions associated with long-distance transportation can be significantly reduced. Combined with walking and biking more often, these small actions can have more meaningful impacts than buying a brand new vehicle.

Tesla Model S 90 D by Peteratkins. Modified by Mariordo

So the next time an electric vehicle advertises zero carbon emissions, think twice about what would actually help the planet rather than buying the newest technology that may not be as green as it seems.

References

  1. Deutsch: Tesla Model S 90 D; 2017.
  2. Ortiz, M. R. D. Electric Car Use by Country; 2019.
  3. Electric Vehicle Battery: Materials, Cost, Lifespan https://www.ucsusa.org/clean-vehicles/electric-vehicles/electric-cars-battery-life-materials-cost (accessed Feb 14, 2019).
  4. English: Cover of the Game “Reduce Reuse Recycle.”
  5. US EPA, O. Global Greenhouse Gas Emissions Data https://www.epa.gov/ghgemissions/global-greenhouse-gas-emissions-data (accessed Feb 14, 2019).
  6. US EPA, O. Greenhouse Gas Emissions from a Typical Passenger Vehicle https://www.epa.gov/greenvehicles/greenhouse-gas-emissions-typical-passenger-vehicle (accessed Jan 24, 2019).
  7. Clarke, S. How green are electric cars? http://www.theguardian.com/football/ng-interactive/2017/dec/25/how-green-are-electric-cars (accessed Feb 14, 2019).
  8. Infographic: The Evolution of Battery Technology https://www.visualcapitalist.com/evolution-of-battery-technology/ (accessed Feb 14, 2019).
  9. Berners-Lee, M.; Clark, D. Manufacturing a Car Creates as Much Carbon as Driving It. The Guardian. September 23, 2010

 

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Posted on January 23, 2019 by in Issues in Science

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Photoswitchable drugs: the light at the end of the tunnel?

Photoswitchable drugs: the light at the end of the tunnel?

For many developed nations, cancer has become the leading cause of death. Regrettably, the current state of cancer treatment still rests heavily on chemotherapy and its toxic side effects. More than ever, our efforts to further develop targeted cancer therapeutics are of paramount importance.

In more recent years, chemists have begun designing light-activated molecules that can be activated upon contact with its target tumor cell and deactivated following cell death.  That said, photoswitchable drugs are not a novel concept; in fact, scientists have been considering synthetic light-switching molecules as promising treatments for blindness, diabetes, Alzheimer’s disease, and antibiotic resistance, to name a few.

Previously, treatments for skin cancer relied on photodynamic therapy (PDT), a process during which patients receive dyes that convert oxygen molecules into their toxic singlet forms capable of killing diseased cells upon activation by light. Given its requirement of oxygen in the body’s tissues, the applicability and potency of PDT are limited by hypoxic tumor environments in which cancerous cells survive without oxygen.

Comparison of (a) classic chemotherapy and (b,c) photopharmacological chemotherapy DOI:10.1002/chem.201502809

Dr. Phoebe Glazer at the University of Kentucky believes that photoswitchable therapies offer a possible strategy for overcoming this restriction. By deriving energy from photons to induce a chemical reaction, photoswitchable therapies enable molecular changes conducive to the recognition and destruction of diseased cells. This approach, unlike current chemotherapy treatments, is capable of killing tumors and saving healthy tissue with specificity, thereby maximizing possible dosage and minimizing dangerous side effects.

Glazer promotes photoactivated chemotherapy drugs that can function as both PDT sensitizers and one-way photoswitches. Using a ruthenium (II) polypyridyl complex, Glazer irreversibly ejected a methylated ligand, and with light, induced the complex to bind to DNA for ultimate cell damage. By modifying the drugs’ ligands, Glazer tuned the molecules’ solubility and the light absorbance wavelength.

ruthenium(II) polypyridyl complexes DOI: 10.1021/ja3009677

Many chemists, including Dr. Wiktor Szymanski at University Medical Center Groningen, are experimenting with molecules that can be switched on and off by light. Once developed, the resulting drugs can be turned on by contact with a targeted cancer cell and turned off after cell destruction. By adding the photoswitchable group, azobenzene, and using UV light to convert the molecule’s configuration, Szymanski produced photoswitchable molecules. 

Photoswitchable molecule developed by Szymanski, Feringa, et al. DOI: 10.1021/jacs.7b09281

Of course, a handful of concerns must be addressed before such “on and off” drugs can become reality. Scientists need to ensure that their switches can work at tolerable wavelengths, specifically ones that can pass through tissue without causing damage. Dr. Achilefu at the Washington University School of Medicine has developed a method called stimulated intercellular light therapy where light is captured by the molecules that target tumor cells. This light has been designed to reach tumor cells beneath the surface of the body (explained in the video below). 

Because of the extreme difficulties and complications related to the synthesis of small molecular drugs, many chemists are skeptical about the approval process of photoswitchable drugs. However, with more research and development, I believe that photoswitchable drugs offer a viable pathway for the future of cancer treatment.

-Brina Kim

 

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Posted on January 23, 2019 by in Uncategorized

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Record Breaking Temperatures in Superconductive Materials

Posted on January 22, 2019 by | Leave a comment

More than 100 years ago a Dutch scientist named Heike Kamerlingh Onnes at Leiden University discovered a phenomenon in mercury know as superconductivity. When cooled to -269°C the mercury exhibited zero electrical resistance unlike conventional materials that release heat when transporting electricity.

Why is this important if it requires such a cold temperature? Over the past 100 years scientist and engineers have incorporated this phenomenon into our daily lives. This allowed for dramatic advancements in medicine such as the development of the MRI. Our power grid also takes advantage of this weird property. However, only select materials exhibit superconductivity when cooled below a temperature referred to as the critical temperature.

An example of a superconducting radio frequency cavity on display at Fermilab made of Niobium, a common metal in superconductivity applications. Source: Wikimedia Commons

In 1987 the technology was revolutionized when a material called yttrium barium cuprate was found to exhibit superconductivity below -181°C. This temperature is easily reached with liquid nitrogen, a widely accessible coolant. This marvelous material has found itself applied at the Large Hadron Collider in Geneva and most hospitals. While materials with higher critical temperatures have been slowly discovered, recent advancements have been shattering the records.

Timeline of Superconductive Materials
Source: Wikimedia Commons

Among these superconductors are a class which only exist at extremely high pressures. The smelly gas that comes from volcanos and is reminiscent of rotten eggs, Hydrogen sulfide (H2S), is one of these. When cooled to -70°C at 1.5 million atmospheres, hydrogen sulfide exhibits an exotic form of high pressure superconductivity. This discovery in 2015 by Mikhail Eremets and Alexander Drozdov at the Max Plank Institute for Chemistry in Mainz, Germany toppled previous records by 39°C, a significant breakthrough in the search for room temperature superconducting materials. Mikhail Eremets said: “Our research into hydrogen sulfide has however shown that many hydrogen-rich materials can have a high transition temperature.”

This has held true with a recently published paper by the same team in December of 2018. Lanthanum superhydride (LaH10) was found to be superconducting at -23°C, however it was at similar pressures to the previous discovery. This value was found to be even higher at -13°C when pressurized up to 2 million atmospheres as published by scientist at George Washington University in January of 2018. Maddury Somayazuli, an associate professor at The George Washington School of Engineering and Applied Science said: “Room temperature superconductivity has been the proverbial ‘holy grail’ waiting to be found, and achieving it-albeit at 2 million atmospheres-is a paradigm-changing moment in the history of science.” Future experiments are expected to provide more breakthroughs in the field.

An engineer at the Advanced Photon Source, part of Argonne National Laboratory where GW University experiments were preformed. Source: Advanced Photon Source Flicker (CC BY-NC-SA 2.0)

While high pressure superconductors lack application, understanding this  property may allow for the development of new materials. With continued research and the recent breakthroughs, the phenomenon of superconductivity may further be propelled into future technology that will have a significant impact on our quality of life.

-Jonah

References:

1.Drozdov et al, “Superconductivity at 250K in Lanthanum Hydride Under High Pressure,” arXiv:1812.0156 [cond-mat], Dec. 2018.                                        2.Somayazuli et al. (2019). Evidence for Superconductivity above 260K in Lanthanum Superhydride at Megabar Pressures. Physics Review Letters, (122), 027001-6.                                                                                                              3.Researchers Discover New Evidence of Superconductivity at Near Room Temperature. (2019, January 15). Phys.org. Retrieved from https://phys.org/news/2019-01-evidence-superconductivity-room-temperature.html                                                                                      4.Superconductivity: No Resistance at Record Temperatures. (2015, August 18). Max-Planck-Gesellschaft. Retriever from https://www.mpg.de/9366213/superconductivity-hydrogen-sulfide                  5.Eck, J. (2018). The History of Superconductors. Retrieved from http://www.superconductors.org/History.htm

 

 

 

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The Awesomeness of Water

Posted on January 22, 2019 by | 1 comment

Think about one chemical used in daily life. I guess most non-chemists would say water. Water is the basic necessity of all living organisms on Earth. It has a very simple structure: two hydrogen atoms stick with one oxygen atom, but it took the Universe 1.6 billion years to make the first water molecule and 13.6 billion years to make water on Earth!

Have you ever wondered why water is so vital to life? One of the answers is proteins. Proteins are the MVP in the body; they do almost everything in cells and make sure tissues to grow and organs to function. Proteins can fold into complex 3D structures, and their biological reactivity depends on how they fold. Although the mechanism remains unclear, studies indicate that interaction between protein and surrounding water controls protein folding. For example, using a theoretical protein-solvent model and a statistical physics approach, Oliver Collet from Nancy University in France suggests that the hydrogen bonding formed between water and proteins promotes fast protein folding as it is relatively easy to break and reform hydrogen bonds at a high temperature.

Protein before and after folding. Image taken from Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/a/a9/Protein_folding.png

In the Catcher in the Rye, the protagonist, Holden Caulfield, wonders what happens to the ducks and fish in Central Park when the large pond freezes. I don’t know about ducks, but I can tell Holden that fish stay at the bottom of the pond and survive over the winter because of the unique thermal properties of water. Hydrogen bonding pushes molecules further apart when water is frozen, so ice is less dense and floats. Oddly, at 4℃, liquid water expands on heating or cooling and has the highest density. This means that water at the bottom is the warmest and maintains a temperature around 4, allowing fish and other aquatic life to survive. In some extreme low-temperature environment, fish use supercooling to avoid freezing. Supercooling is when water is cooled below -40℃ without freezing, and you can even try at home.

How to make supercooled water at home. Video taken from YouTube

Although water is largely used as a solvent in most reactions, it has been found that water can act as an electron donor for certain biocatalytic reactions, enabling more efficient and greener synthetical routes. Avelino Corma, Frank Hollmann and co-workers report water as the electron donor for biocatalytic redox reactions using enzymes, like oxidoreductases. Despite the requirement of additional energy, activation of water as an electron donor is a common natural process: photosynthesis where visible light provides energy to promote water oxidation, generating oxygen along with electrons and protons. Inspired by nature’s method, the researchers come up with a strategy to accelerate water oxidation using photocatalysts, in this case, metal-doped TiO2.

As water is so common in our daily life, it is often underappreciated. It facilitates not only biological activities but chemical reactions and ensures all creatures to survive even under the harshest conditions on Earth

Reference:

Francl, M., Nature Chemistry, 2016, 8, 897-898

Collet, O., J. Chem. Phys, 2011, 132, 085107

Chaplin, M., Water structure and Science, http://www1.lsbu.ac.uk/water/water_anomalies.html#j (accessed Jan. 20, 19)

Supercooling, Wikipedia.org, https://en.wikipedia.org/wiki/Supercooling (access Jan. 20, 19)

Mifsud, M.; Gargiulo, S.; Iborra, S.; Arends, I.W.C.E.; Hollmann, F.; Corma, A., Nature Communications 2014, 5, 3145

 

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A Potential Memory Enhancing Drug

Do you easily forget things? Would you like to improve your memory? A recent study led by Professor Yuji Ikegaya and Dr. Hiroshi Nomura of the University of Tokyo suggests that your long-term memory might be improved with pro-histamine treatment.

The structural formula of histamine. Retrieved from Wikipedia Common.

Pro-histamine drugs increase the level of histamine, which in the central nervous system is associated with learning and memory. Scientists believe that elucidating the role of histamine in memory may help alleviate the symptoms of dementia.

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Posted on January 22, 2019 by in Biological Sciences

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