Auroporis: The Trojan Horse of Cancer Treatment
Imagine a city. Not just any city, but a city infested with killer robots! Currently, they are small in number but each day they multiply so that they can eventually achieve their goal, to destroy the entire city. You’d think as humans with all sorts of weapons, we could defeat these robots but there’s a catch. These robots are indistinguishable from humans. Now attacking them gets harder as we can't tell if we are actually getting a robot or a healthy human.
Now luckily we don’t live in a society like this, at least I hope not. But as humans, there is a similar situation that affects many of us every day. Cancer.
Cancerous Robots
Our body grows through the multiplication of cells. One divides into two, two into four, and so on. Luckily for us, the DNA in our cells has instructions to tell the cell to stop dividing when there is no need to do so anymore. Unfourtantly, some of these cells have faulty instructions, so they are never told to stop. These cells become cancerous and are responsible for the formation of tumors.
Cancer is different from a normal disease like the cold, or strep throat because it’s our own cells causing the problem, not some foreign virus or bacteria. This means it’s much harder to distinguish between our healthy cells and the tumor cells. Our healthy cells are like the humans in the city while our cancerous cells are like the killer robot look-a-likes.
This causes a problem with current methods of cancer treatment such as chemotherapy, the use of drugs to chemically destroy tumors, and radiation therapy, the use of high-energy waves to penetrate and destroy tumor cells. While these methods are successful in destroying tumors, they are also successful in destroying healthy tissue, which causes a load of problems for the patient.
Using these methods is like trying to get rid of the killer robots by nuking the whole city, or releasing tear gas into everyone’s home. Were killing the robots, but also the humans.
It’s clear that if we want to improve cancer treatments, we have to make them more selective in which cells they destroy. That’s where Auroporis comes in.
Auroporis
“Auroporis” is a company created by me and my co-founder, Stephanos Firku. As a company, our mission is to create more targeted cancer therapies, specifically for pancreatic cancer, using the plasmonic properties of gold nanoparticles along with the targeting properties of specific growth factors. Now that’s a bit of mouth full, so let's go over each part.
Due to the low survival rate of pancreatic cancer, and the low effectiveness conventional methods have on the treatment of pancreatic cancer, Auroporis’ early research into this technology will be for the treatment of PC. Because of this, much of the information will be referencing protiens specific to studies on pancreatic cancer.
Targeted Delivery
So imagine in our dystopian city, a mad scientist discovers something that could help distinguish killer robots from humans. He finds out that killer robots often have large amounts of oil in their homes. Makes sense considering they are robots. So if you were to randomly sample homes and apartments across the city, those with a high amount of oil cartons are likely to belong to killer robots.
Although hard to see from our perspective, tumor cells have a similar property. Because these cells are ordered to grow and divide much more than the average cell, they end up containing a lot more “growth proteins” than are found in normal healthy cells. For example, it was found that pancreatic cells that became cancerous (SW1990 cells and PANC-1 cells) had a significantly larger concentration of urokinase plasminogen activator receptors (uPAR) than healthy pancreatic cells (HPDE6-C7). uPAR is a protein made in cells to help induce cell growth, and when the instructions in the DNA to limit the production of uPAR are inhibited, the protein is overexpressed.
So uPAR is like the oil in our city. If there is an excess amount of it in a cell, it is likely a tumor cell. So how does knowing this help us kill the cell?
Going back to our city, by knowing that robots order a lot of oil, we can hide things inside the oil cartons such as a bomb. This way, when the robots willingly bring these cartons of oil into their homes, they will also bring in a bomb that will kill them without harming the humans nearby. Similar to how the trojans defeated the city of Troy with their trojan horse.
The same thing can be done with cancerous cells. By attaching drugs to proteins that are overexpressed in cancer cells (such as uPAR), the cancer cells will naturally draw in these proteins along with the attached drug. This is where gold nanoparticles (GNPs) come in.
Creating the “Bomb”
GNPs are very useful for targeted drug delivery due to the negative charge on their surface. This allows us to easily attach proteins and biomolecules to the particle, such as the drugs and proteins mentioned before.
But, GNPs also have a very interesting property that has been of increasing interest to researchers recently and that’s its ability to absorb light and create plasmonic oscillations.
“Plasmonics” is the field of physics involving electron oscillations of metal nanoparticles. Each nanoparticle has a wavelength of light that resonates with it most, and this wavelength value is affected based on the size and shape of the nanoparticle.
When the light of this resonant frequency is shined onto a nanoparticle, it causes the electrons in the particle to move from one side to the other, following the pattern of the wave. These oscillations of electrons from one side to the other are called plasmons. These plasmons create localized heat surrounding the nanoparticle.
Photothermal therapy is the process of using this heat to kill cancer cells. By attaching nanoparticles to these targeting proteins (uPAR for pancreatic cancer), we can sneak them into the tumor cells, just like the bombs in the oil cartons. We can then externally shine resonant light over this area of the body, causing plasmons to form on the nanoparticles resulting in heat great enough to destroy the cell it resides in. This allows for the targeted destruction of tumor cells while still protecting the healthy cells.
Proof of Concept
This process is currently being tested in vivo and in vitro on mice. In “A Comparative Study of Clinical Intervention and Interventional Photothermal Therapy for Pancreatic Cancer,” this process is done using spherical gold nanoparticles coated with uPAR, polyethylene glycol (PEG), and indocyanine green (ICG). PEG is a compound used to keep the particles in the body longer while ICG is a dye used for its fluorescent properties to track the movement of the particles. From this, we can see how these nanoparticles act like a car in which many different types of drugs and trackers could be loaded onto it.
These “upgraded” GNP’s were injected into mice with pancreatic tumors. Using photothermal therapy, they were able to show how these GNPs had a significant effect on the tumors, getting rid of them 6 days after the initial treatment, while typical radiation therapy was shown to have little to no effect at all after 15 days. Furthermore, after around 55 days, the percent of mice that had radiation therapy that survived was 0% while around 40% injected with the GNPs were still alive after 60 days.
According to the paper:
“As a result of the feasibility and effectiveness of this therapy, it is likely that this minimally invasive uIGN-mediated IPTT method could be translated into clinical practice in the near future, particularly for aged and/or high-risk patients, or for patients who develop metastases.”
At Auroporis, our goal is to do further research on photothermal therapy to create an injection of coated gold nanoparticles that could be used in tandem with near-infrared light rays to help treat those with deep-buried pancreatic cancer. What Auroporis plans to do differently than the bulk of current research is to optimize the process by using it in conjunction with chemotherapy drugs.
Photothermal + Chemotherapy
While photothermal therapy has been showing a lot of promise in studies on mice and isolated human cancer cells, there remain some deficits in its abilities.
In the paper “Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer,” it is addressed that photothermal therapy while getting rid of large chunks of tumors, can often leave residual tumors behind if the tumor cells were sporadically dispersed. The paper goes further into talking about the synergistic effects of combining photothermal therapy with chemotherapy.
In the study, spiky gold nanoparticles were coated with polydopamine (PDA) to help contain the structure of the particle when traveling through the body, along with doxorubicin which is a type of chemotherapy drug. These particles were then sent into colon cancer cells in animals, and photothermal heating took place. The combined effects of the heating from the GNP and the drug doxorubicin showed complete destruction of the tumors in more than 85% of the animals tested on.
Even better were the immunological effects that occurred. These animals that had their tumors destroyed showed significant resistance to tumor regrowth in the area treated, after just one therapy session. The best part was that lower dosages of doxorubicin were necessary, compared to traditional chemotherapy, further decreasing the chances of healthy cell destruction.
These studies are promising and Auroporis hopes to speed up the development of this research so that the process can be used clinically for humans.
Auroporis: Key Focus
Auroporis’ main focus of research consists of:
- Focusing on pancreatic cancer and researching the growth proteins that would identify pancreatic tumor cells specifically.
- Researching different sizes and shapes for the GNP itself to find out which ones are the most biocompatible, stay in the body for the right amount of time, and produce the most heat for the least amount of energy.
- Experimenting with different types of FDA-approved chemotherapy drugs to attach to these GNPs as an added anti-tumor component, along with different dosages to see which one has the biggest effect on tumor cells while decreasing its effect on healthy cells nearby. Drugs of interest include Gemcitabine and 5-fluorouracil.
The Cost
The current cost for full chemotherapy treatments can range from $10,000 to $200,000. More specifically, the cost of Gemcitabine for a full treatment of chemotherapy can range from $5,043 to $67,216. Radiation therapy, based on the type of cancer, can range from as low as $8,600 to around $25,000 for the full treatment. In other words, cancer treatment is very expensive.
The company “Nanopartz” sells dosages of gold nanoparticles that come in a range of prices from 350$ to 2,500$. These include dosages good enough for up to five injections in mice. This helps to give an estimate on how much GNP synthesis is right now.
We believe the cost will go down through our own synthesis of GNPs along with the growing research in decreasing the cost of GNP synthesis for mass production.
With this in mind along with the fact that chemo-photothermal therapy would require fewer total sessions for treatment, possibly even one, and the fact that a significantly lower dose of chemo drugs such as Gemcitabine is needed, we believe we can drastically reduce the cost over time in comparison to traditional methods, making more efficient and targeted treatment at a lower cost.
Ultimately Auroporis wants to help those with cancer get a more targeted treatment with less necessary time in the hospital. The future is becoming more precise in the technology being used, and cancer is no exception. The best way to beat cancer is at its scale, and we believe that the use of GNPs for targeted chemo-photothermal therapy is the most promising method to do so as of now.
We hope with this technology we can safely rid our city of these killer robots, keep our humans safe, and protect our city.
