Apollo Therapeutics — Shining a Light on Cancer Treatment with Nanotech
Tell me, what do you actually know about cancer?
Everyone hears about cancer right from when we’re little. It’s been a steady part of modern society and as elementary kids, we come to fear hearing the very word. The word leukemia, a deadly cancer occurring in the blood, brings out the worst connotation.
But as much as we fear cancer and leukemia, within every right, of course, I have a feeling you don’t know as much about them as you could. Because the more you know about leukemia, the more you begin to realize that there are several issues in the current treatment.
Issues that we believe can be eradicated by leveraging nanotechnology that may seem like something out of a sci-fi novel but stay with me, improved cancer treatment is not a fantasy.
What Are We Up Against?
To understand where the future of cancer treatment lies, we have to understand the issue we’re facing. So let’s start with: what exactly is leukemia and why leukemia?
What makes leukemia so different from most cancers is the fact that this particular cancer starts in the bone marrow and then seeks to spread throughout the body, sometimes even leaving the bone marrow into organs, such as the liver and spleen. Many other cancers start in these specific organs and will spread throughout the body, sometimes going into the bone marrow. This means that leukemia is able to start in any place of body; it just has to be in the marrow. Leukemia is also one of the few cancers that doesn’t form a tumor, making it that much easier to target a specific site to treat.
This deadly stem of cancer affects the blood and bone marrow in the body. While it can spread, leukemia begins in a cell in the marrow. After being infected, the cell undergoes a change that will result in the leukemia cells growing and getting even stronger; the cells will survive better than normal cells in the bone marrow. While white blood cells are usually seen as the “fighter cells” but due to leukemia, the bone marrow tends to produce excess abnormal cells; these cells don’t function properly relative to non-cancer cells.
To give you an understanding now how dangerous this cancer can be, let’s run through some stats. Every year an estimated 61, 780 new leukemia cases are diagnosed in the United States and every single year, almost 23, 000 are estimated to die fighting the disease. The survival rate over the course of 5 years is just barely over 60%. And while that may seem like a positive statistic, this means that over 100,000 die of leukemia over the course of those 5 years.
That is over 100,000 people that can be saved. That is enough people to fill in the Michigan Stadium, the largest American football stadium.
There are many different types of leukemia. The most common type that impacts adults (aged older than 19) is chronic lymphocytic leukemia or CLL. This branch of cancer is responsible for around 38% of all leukemia diagnosis in adults and is estimated to kill over 4,000 people just in 2021.
Let’s dive a little deeper into CLL so we can better understand the faults in its treatment.
CLL is a chronic leukemia which (yes, it’s definitely as bad as it sounds) means it’s just that much harder to cure. Diagnostic tests for CLL look for a lack of the proteins ZAP-70 and CD38. ZAP-70 is responsible for the activation of T-cells, major fighters in the immune system. The latter protein is found on the surfaces of many cells in the immune system, specifically B-cells, another integral part of the body’s defense system. This information is vital for later when we discuss how Apollo Therapeutics technologies will help eradicate the threat of CLL.
These specific cancer cells look very similar to normal blood cells but they definitely not. Unlike normal blood cells, these leukemia cells don’t actively fight infection and they tend to survive much longer. CLL cells are not to be confused with cells from lymphoma. Lymphocytic cancers are, like mentioned before, usually found in the bone marrow and blood. On the other hand, lymphoma cancer cells are found mostly in the lymph nodes and tissue.
Since CLL is most common in adults, the risk of getting this specific type of leukemia increases the older you get. 90% of CLL patients are usually older than 50-years. There is also a correlation between the exposure of chemicals and the risk of CLL; long-term exposure of chemical fumes will potentially lead to increased risk of CLL. Similar to many diseases, experts say that inherited genes play a stronger role in increasing the chances of CLL than most would assume. Yet this also contradicts the fact there are more cases of CLL in North America and Europe as opposed to Asia.
Regardless of these factors, CLL still accounts for 100,000 people who lose their lives to this disease. And that’s just in the United States.
But to fix an existing issue, we need to see what’s wrong in the treatment. For that, we have to go into how CLL is being treated right now.
Cancer Treatment is Not Enough
Now leukemia in general can be treated in multiple ways, including radiation therapy, bone marrow transplant, chemotherapy, targeted therapy, immunotherapy, engineered immune cells, or even various clinical trials. For sake of relativity, let’s double click on treatment through chemotherapy, the most common treatment for leukemia. In most cases, the chemo drug(s) are delivered through a pill or an injection into a vein.
Many in modern day society are familiar with the concept of chemotherapy, a common procedure used to treat cancer. On average, a treatment using chemotherapy will last around 6 to 12 months or longer. The side effects from the drugs are far too severe for some treatments to be given on an everyday basis.
The treatment details, such as the certain drugs, the dosage, and treatment schedule, can vary depending on many factors:
- Type of cancer
- The stage of cancer — including the tumor size, location of the tumor, and where or if it is spreading through the body
- Age and the general state of health of the patient
- The patient’s ability to cope with the side effects
- Previous medical conditions — high blood pressure, heart disease, diabetes, kidney disease, arthritis, among many others can lead to negative reactions to chemotherapy
- Any previous cancer treatments
Chemotherapy 101
Chemotherapy can be used in 3 different ways. Neoadjuvant chemotherapy is used to shrink cancer tumors in preparation for other means of cancer therapy. It is most often used before tumor removal surgery or radiation therapy. Adjuvant chemo is used to kill any remaining cancer cells. In contrast to neoadjuvant therapy, this method is used after tumor removal surgery or radiation therapy. Think of adjuvant therapy as almost a clean-up crew making sure all the tiny leftover cells are taken care of. Lastly, chemotherapy can be used plainly as treatment. This is mostly used for recurrent cancer (cancer that came back after being treated) and/or metastatic cancer (cancer that spreads throughout the body).
Currently, chemotherapy can be taken in multiple ways. A common drug delivery system (DDS) entails injecting the chemo drugs directly into the vein (intravenous (IV) chemo), the artery (IA chemotherapy), or plainly injected into the muscle or under the skin, usually in the arm, leg, or abdomen. Other DDS’s include chemo drugs being directly placed on the abdomen or peritoneum mostly for cancer treatment for ovarian, stomach, or liver cancers. Topical therapy is also frequently used; chemotherapy drugs are taken through a cream that’s applied onto the skin. The most frequently used DDS is an oral chemo. This delivery system, quite simply, has the patient swallow a pill, capsule, or liquid. Certain drug delivery systems require different treatment schedules depending on the dosage of the chemo drugs which can result in varying negative side effects.
When treating CLL specifically, scientists tend to use 3 classes of drugs: purine analogues, alkylating agents, and corticosteroids.
- Purine analogues — antimetabolites that slow the metabolic processes of cancer cells, slowing down the growth of the cancer
- Alkylating agents — they add alkyl groups to the guanine base in the DNA of the cells, preventing the double helix from linking to other structures effectively breaking down the DNA of the cancer cells
- Corticosteroids — hormones that help regulate bodily functions to reduce sickness but can also weaken the immune system after a bone marrow transplant for easier acceptance of the marrow
The most commonly used drugs are fludarabine, cyclophosphamide, and rituximab. The first two drugs correlate to the first two classes listed above: fludarabine being a purine analogue and cyclophosphamide being an alkylating agent. The third, rituximab, is not a corticosteroid, but a newer type of drug, a monoclonal antibody, that is more commonly used by experts, yet it is sometimes used in a combination with steroids. This 3-way combination is often called FCR, and it most commonly used for the initial treatment of CLL.
Chemotherapy drugs do not actually target cancer cells specifically. It sounds crazy but stay with me, it’ll make more sense in the end. These drugs are made to target any fast-spreading cells. Cancer, at the roots, is the unhealthy growth of abnormally functioning cells. While it seems reasonable to have chemo target fast-spreading and growing cells, there’s huge backlash for this. See, cancer cells are not the only fast-spreading cells in the body. Cells found in the bone marrow, cells lining the intestines and mouth, and cells in hair follicles are also (unintentionally) targeted by chemo drugs due to the fact that they grow and spread at much quicker rates compared to the average cell in the human body.
Due to these other cells being targeted, patients undergoing chemotherapy will experience lots of side effects which are discussed in detail soon. Essentially, the chemo drugs are also harming the body while attempting to cure cancer. Modern-day chemotherapy often allows the drugs to circulate the bloodstream, which means the drugs tend to linger in the body long after the treatment is over.
While chemotherapy is one of the most frequently used methods of cancer treatment, there are MANY negative side effects from the drugs. Common side effects include nausea, vomiting, diarrhea, hair loss, loss of appetite, fatigue, fever, mouth sores, pain, constipation, easy bruising, bleeding… just to name a few. Luckily most of these “minor” side effects tend to disappear over time after the treatment is over and some can even be prevented. Unfortunately, there are also major effects that don’t tend to show up until a month or two after the treatment is over. Effects under this category can be anything from damage to lung tissue, kidney problems, nerve damage to heart problems, infertility, and even the risk of second cancer.
Wild isn’t it? The very treatment that’s supposed to help get rid of cancer has the possibility of causing MORE cancer?!
It’s about time something changes in our medical industry.
Apollo Therapeutics’s Vision
At Apollo Therapeutics, we strongly agree that the status quo of cancer treatment needs to be upgraded. We are not aiming to replace chemotherapy but rather Apollo Therapeutics’s quantum technology will revolutionize the effectiveness of chemotherapy.
Once Apollo Thereapeutics’s technology has been implemented around the world in hospitals, we see a world where the threat of cancer is equal to the threat of the common cold. We realize eradicating cancer can be a daunting proposition but minimizing the risk of cancer is entirely possible with our technology. With quantum dot bioconjugates, chemo drugs will be specifically targeted at the tumors and lessen the severity of the regular side effects of the regular chemotherapy, possibly even preventing the side effects altogether.
An Introduction to Quantum Dots
Quantum dots, referred to throughout this article as “QDs”, are nanoscale crystals that can transport electrons. QDs are also known as semiconductor nanocrystals and have multiple applications across many different disciplines including biomedicine, green energy (solar cell development), electronic displays, and other photodetector devices. Quantum dots range in size between 2–10 nanometers and have properties like light absorption and fluorescence. Their biggest property and the one most beneficial to industrial use is their size and versatility in function due to unique shape and high surface area ratios. Because of their properties and size, QDs are often referred to as artificial atoms and by making conjugates of these nanoparticles, they can essentially become artificial molecules.
QDs primarily function by harnessing light from the electromagnetic spectrum and containing that light to be released later on while maintaining strong brightness. When quantum dots are illuminated by a light source, electrons within the valence band of the structure will transfer to the conduction band, releasing light as the electrons become unexcited. But to understand the photoelectric properties of quantum dots and so forth, it is important to first understand the electronic composition of solids and thereby QDs.
Every solid contains a valence band and a conduction band. These two layers of molecular composites determine the electronic potential of a solid as well as how energy is transferred throughout. The valence band is the outermost atomic layer of a solid (hence the name valence, like valence electrons of an atom.) It has the highest number of electrons and electronic energy levels within. The conduction band, the inverse of the valence band, has the lowest electronic energy and number of electrons within the solid. The distance between these two bands is called the bandgap and this is where the photoelectric and optical properties of quantum dots are dependent.
Quantum Dot Structure & Composition
As quantum dots are semiconductors, energy levels being shone upon them can cause electrons to jump across the bandgap and thereby release photons, or in other words, light equal to the intensity that it was shone with. According to quantum mechanics, the energy of photons released is relative to the wavelength of the photons, and thus the band gap is an enormous determiner in this kind of energy. Because quantum dots are much smaller and are made with multiple atoms, the size of quantum dots determines the size of band gaps. For example, smaller quantum dots have larger band gaps which means more energy is released, therefore the higher the frequency, and so more bluish colored light is released. Along with size being an important determiner of quantum dot functions, the structure is also important. For example, is it solid or hollow? This can determine the potential functions of the QDs as well as structural/physicochemical integrity.
Now, the structure of quantum dots is quite important given that it can determine the function and overall application potential of the QD. But the general structure of quantum dots includes three primary components:
- Semiconductor Core — is the center of the quantum dot and contains the main component of the quantum dot.
- Shell — acts as a protective layer over the core that stabilizes radioactivity of photonic release as well as balances physical integrity.
- Cap — outermost layer that protects the entirety of the quantum dot and consists of ligands (ions or molecules that are attracted or completely unattracted to other molecules) that protect the QD as well as its environment.
In addition to the structure of a QD determining function and overall potential, the materials utilized to create a quantum dot also play an important role. There are two subgroups of elements that most quantum dots are most commonly composed of:
- II-VI subgroup — II portion includes substances Zinc and Cadmium; the VI portion includes elements Oxygen, Sulfur, and Selenium.
- III-V subgroup — III portion includes elements Boron, Aluminum, and Gallium; the V portion includes elements Nitrogen, Phosphorous, and Arsenic.
The portions of the groups match up with each other. For example, cadmium and selenium from the II-VI subgroup would match up to compose the core of a CdSe (cadmium selenide) quantum dot, and zinc and sulfur would match up to compose the shell of that same CdSe quantum dot. The compound components of the shells of quantum dots are dependent upon the application those quantum dots will be utilized for. However, the II-VI group is most effective in photoelectric applications.
There is an outstanding amount of potential applications of quantum dots, some of which are already being implemented and utilized today. For example, quantum dots have been used widely and massively for digital displays, heightening color depth and developing “Next-Gen Displays.” This is because QD materials have purer colors, longer lifetimes due to photon conservation, lower cost for manufacturing, and low power consumption. However, the biomedical potential for quantum dots is largely developing still and is primarily used for bioimaging and biosensing/immunosensing. Because of their photo-optic capabilities, using quantum dots to map out parts of the human body like tumors is widely implemented. They are used as organic dyes in biological research, but one of the greatest potentials of these man-made nanoparticles is within the oncological field and direct drug delivery.
Quantum Dots & Oncological Drug Delivery
Nanotechnology, or nanotech for short, describes the manipulation and optimization of materials with dimensions less than that of 100 nanometers (hence the name “nano.”) This branch of materialistic technology has many applications including harnessing green energy, developing advanced computational systems, and even advancing medicine. Implementing nanotech within the medical space is one of its greatest potentials; specifically utilizing this tech for drug delivery systems. Quantum dots fall underneath that kind of tech that can be best optimized for DDS and the biological conjugation of such can immensely advance this field due to their beneficial size, making passage of membranes feasible and thereby targeted delivery more effective.
Drug delivery systems are techniques utilized to enhance the efficacy and accuracy of pharmaceutical treatments. There are many different kinds of DDS including digestion, inhalation, intravenous injection, skin absorption, and most interestingly, nanotechnology. Different forms of drug delivery systems are used and optimized for the drug and disease being targeted and because of this, efficacy and accuracy are improved for medication intake.
These kinds of systems help not only to better the efficacy and accuracy of drug treatments but also to reduce side-effects of mainstream treatments for different illnesses. For example, cancer is one of those illnesses with severely adverse side-effects from treatment (chemotherapy), already described in this article. By utilizing DDS, the side effects here can be reduced and overall make treatment more effective. Cancer treatment utilizing nanotech-based drug delivery systems is an immensely promising field, and by utilizing quantum dot technology, this field can be further expanded.
Quantum dots in the biomedical field have been used for things like biological dyes as well as bioimaging and immunosensing. Bioimaging is a process by which biological systems can be seen and/or even be photographed to better understand how they are functioning; immunosensing is being able to detect and understand the immune system of an organism. QD’s (quantum dots) do this sort of thing by being engineered to maximize their photoelectric properties and by using targeted systems used in forms of DDS. However, what if they were used not only to identify and mark biological bodies but also to deliver treatment to disease? And even optimize this system for treating one of the most ravaging diseases: cancer?
QD’s in oncology has been one of the most explored applications of quantum dots due to the need for improvement in the field of cancer identification. Multiple studies have done experimentation and research utilizing quantum dots to improve that very same field.
One such study [1] was done by scientists at the Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China. They found that “Ultimately, QD nano-carriers for drugs can enhance the efficacy and reduce side effects of drug reactions to improve the therapeutic index of the drugs.” This is representative of multiple factors including the fact that quantum dots provide multiple benefits including their versatility. Versatility is important when it comes to bioconjugation (the bonding of an inorganic and organic molecule to form a system).
Another study [2] was performed by multiple biotechnology institutions regarding quantum dots for biosensing for the detection of Lung Carcinogenesis miRNAs. A great benefit of utilizing quantum dots as bioimaging nanotechnology is their high surface-to-volume proportion which makes them highly receptive to different manipulatory procedures, tying back to their versatility when it comes to bioconjugation. This is really important as making quantum dot integration across multiple systemic pathways can only be accomplished if other biological components can be interchanged and manipulated to match those pathways.
A third study led by Dr. Sarwat Butool Rizvi [3] included utilizing near-infrared QD’s for HER 2 localization in breast cancer. This study was important in understanding further just how exactly QD nanotechnology can be targeted to specific parts of the body, definitely important when it comes to targeting diseases as specific as cancer. HER 2 is a specific protein that the near-infrared QD bioconjugates searched for as that specific protein is what encoded the breast cancer mutation. This particular utilization of QD’s in the study concluded the idea that the versatility of the nanotechnology of quantum dots was immense as virtually any ligand can be bound to QD’s which allows for direct delivery of simply the quantum dots, or even in theory, entire drugs/medications.
Overall, quantum dot bioconjugation for targeted travel throughout the body is entirely possible, but the possibilities of this process is highly speculatory in the sense of feasibility. We are able to isolate and even detect specific markers or ligands (molecules that bind to other molecules; often conjugated for targeted access) but the entire possibility of drug delivery is more so a probability rather than completely feasible due to multiple restraints. However, there are also multiple methods/designs that have been drafted and speculated towards this sort of development. The primary accessories to the quantum dots within these bioconjugate models include ligands, amphiphilic polymers, and antibodies.
Ligands are molecules that bind to other molecules. When conjugated with quantum dots, they are, in essence, the driver of the bioconjugate minivan. Because ligand molecules attract each other, when we talk about direct delivery, they play a humongous role in targeted travel to certain cells or tumors. For example, in order to directly deliver chemotherapy to a type of cancer (specifically leukemia), we would have to send the bioconjugate to cancerous cells. In order to do so, the ligands on the outermost part of the system would have to direct, or in other words, drive the chemo drugs to those cancerous cells.
This would happen, particularly in Apollo Therapeutics technology, by searching for and binding to missing genetic material that the ligands would code for in cancer cells. The ligand differs entirely by what is being targeted but some examples of types of ligands include nucleic acids, proteins, amino acids, or even just strands of inorganic molecules. Regardless, ligands tell the system where to go and are immensely important.
Amphiphilic polymers are macromolecules (very large molecules made of covalently bonded atoms) that contain both hydrophobic and hydrophilic parts. Hydrophobic means that the part of the amphiphilic polymer repels water and does not mix with it. This is especially important for parts of cells that do not want to get wet in order to maintain stability. For example, the cellular membrane of a cell is made up of a phospholipid bilayer, which is a kind of amphiphilic polymer. The inner part is hydrophobic so the cell remains intact and is not affected by the aqueous environment of the body. Hydrophilic means that the part of the amphiphilic polymer is able to be in the water and does not repel it; essentially it is the opposite of hydrophobic. The outer part of the phospholipid bilayer aforementioned is hydrophilic since the cell is in an aqueous environment.
When amphiphilic polymers are applied to quantum dot bioconjugates, or QDBC’s, they can come in the form of micelles or liposomes. They serve mainly the purpose of coating QDBC’s so that they are safe for the body, and also to store the cargo that the QDBC is carrying. Micelles are molecules that have a hydrophobic tail and hydrophilic head. However, unlike a phospholipid bilayer, the outer part is hydrophilic and the inner is hydrophobic and has no second layer. It is a monolayer, not a bilayer. This is more of simply an encapsulator, rather than a complete layer.
Liposomes are quite similar to phospholipid bilayers in that there are two layers of phospholipids, with one having the hydrophilic head on the outside and hydrophobic tail on the inside, and the second layer being complimentary for that. Both serve similar purposes but the use is dependent on the cargo being delivered by the QDBC.
Antibodies are proteins developed and utilized by the immune system to identify and destroy foreign objects to the body such as viruses or bacteria. In the case of quantum dot bioconjugates, these proteins are often placed in the same layer as ligands in order to make sure the immune system does not destroy the QDBC. This added layer prevents attack by the immune system as well as a more clear route to cellular transport given that obstacles are not as difficult to cross like immune cells.
Now that we understand the biological aggregations of quantum dot bioconjugates, we can look at different models of these kinds of systems and observe current predictions to understand how exactly DDS can be implemented to treat cancer. Three examples as follows:
Model 1:
Model 2:
Model 3:
All of these examples display how exactly a QDBC would function at the microbiological scale and by manipulating these models, different results can be produced for different functions. Utilizing systems like these, we can develop a new form of DDS (direct delivery system) to treat cancer, specifically leukemia. Overall, we can redefine quantum dot applications within the biomedical field, expanding to actual oncological treatment. We call this endeavor: Apollo Therapeutics.
Apollo Therapeutics
Apollo Therapeutics is a moonshot startup focusing on treating leukemia like the flu. By developing quantum dot bioconjugates (what we like to call QDBC’s), we can create a DDS (drug delivery system) beneficial for treating the highly specific cancer of chronic lymphocytic leukemia that has affected millions.
Quantum dots, aforementioned in this article, are nanoscale crystal structures ranging from 2–10 nanometers that transport electrons. These nanotechnological masterpieces have a myriad of applications but what we at Apollo Therapeutics hone in on is their potential in the biomedical field; specifically, in oncological treatment. And even more specifically, to treat CLL leukemia (chronic lymphocytic leukemia.) Specificity is an immensely important part of solving the issue of indirect delivery that supposedly treats cancer. And in order to do this, we must develop QDBC’s for DDS of chemotherapy. But first, why quantum dots? Specificity is important, so why would quantum dots fit the necessary components of an effective DDS?
Criteria that we have established for an effective delivery system via quantum dot bioconjugation is based upon the three studies aforementioned (1, 2, 3.) These include:
- Needs a high drug loading capacity — in order for the QDBC DDS to be most effective, there must be a high potential for utilizing and maximizing the drug space of the conjugate.
- Must have high encapsulation efficiency — for the targeted delivery to make it to the target, drugs/other cargo must remain intact and remain functioning by the time of release inside of the target.
- Good biocompatibility — the components of the QDBC must remain biocompatible and not completely harmful to the body while still remaining effective through crucially selecting materials.
- Low toxicity — because quantum dots contain heavy metals, fallout of those heavy metals can be harmful in large quantities (5mg/liter of blood before death) so monitoring how fallout is to be contained, as well as low toxicity in initial materials is important.
Because quantum dots are highly versatile [3], the capabilities of customization are very promising, and so the criteria of an effective delivery system can be met utilizing different accessory components.
Understanding Apollo Therapeutics’s Bioconjugate
This kind of customization is based on multiple different studies and trials that have been run to better understand quantum dots in targeted transport throughout the body. We have drawn up a schematic of how exactly this bioconjugate delivery system would function, including what the QDBC would be composed of. Components of the QDBC would include the quantum dot, ligands, amphiphilic polymers, antibodies, nuclear localization sequences, and compound chemotherapy (CC). The schematic of our quantum dot bioconjugate system is as follows:
The quantum dot holds the core of the bioconjugate as it is the substance, if you will, of the delivery system. It holds the shape and base upon which to bioconjugate the delivery vessel. It will also serve the purpose of sub-cellular labeling which will, by harnessing the photo-optic properties of QD’s, help track the efficacy of treatment as well as the advancement of cancerous growth if any. The quantum dot has many advantages it in bioconjugation and specifically for DDS.
One of the biggest advantages of utilizing QDs is their ability to easily cross cell membranes. This allows QDs to penetrate specific target sites in the human body and easily gain access to in our case, cancerous cells. This also means that the CC within the QDBC will be fast-acting and treatments can be done accurately unlike ineffective cancer treatments like chemotherapy as it is done today.
QDs also have a very high specific surface area which provides multiple attachment sites for drug targeting. Again, this allows for precise drug delivery to specific cancerous cells. This is why sizing of the bioconjugate is crucial to the efficacy of the DDS. In our model, the quantum dot is the smallest possibly made (2 nm) in order to maximize the drug space within the QDBC. This way, with high surface area, sizing of the quantum dot can be manipulated without losing much of the surface, bioconjugation properties that would make it effective.
In addition to both having an optimal size for cell membrane passage and having a high surface area, quantum dot nanotech has an outstanding photo-optic array of capabilities, aforementioned in this article. Because of this, when implementing QDs into the QDBC, we could kill two birds with one stone if you will, by first using the QD as a drug delivery probe, but also to leave it in the cell and utilize its photoelectric properties for imaging. By first charging the quantum dot with ultraviolet light, utilizing different x-ray or imaging systems, we can observe both the advancement of cancer, as well as the status of the drug’s efficacy.
Ligands as described earlier in the article are ions or molecules that are attracted or completely unattracted to other molecules. Aforementioned, ligands are essentially the driver of the bioconjugate minivan as they are the molecules of the QDBC that know where to take the rest of the components. This property allows for targeted therapy to be even more accurate given that ligands can search for specific markers of cells that are being targeted (like leukemic cells). In this particular case, for Apollo Therapeutics’s QDBC DDS, ligands that are attracted to specific molecules will be utilized. More specifically, ligands which are attracted to the gaps made in the cellular protein make-up by the lack of ZAP-70 and CD-38 proteins in leukemic cells. Because leukemic cells have a mutation that causes the lack of those proteins, by targeting these specific gaps, the efficacy of the targeting system of Apollo Thereapeutcs’s QDBC DDS can be maximized in two aspects.
First of all, just having an identifying marker is already a beneficial aspect. Because ligands are attracted to certain molecules, in this case, protein chain gaps, they will move towards those gaps and thereby carry the entire bioconjugate and in this specific case, to leukemic cells in the body. In unison with the nano-aspect of quantum dots, traveling towards the direction the ligands are driving can be accomplished.
The second aspect by which the ligands of the QDBC are effective is the fact that in order for anything to enter a cell, receptors must “allow” entrance. This is due to cellular membranes being semi-permeable, meaning that there is selective exit and entrance to the cell. By having ligands specifically searching for gaps in proteins, receptors on the outer part of the cell are able to connect to those ligands and allow the bioconjugate inwards. By accomplishing this important role of the process, the DDS is most effective, and targeted delivery can succeed.
The amphiphilic polymers (polymers/membranes that contain both hydrophobic and hydrophilic components) in the QDBC would include primarily liposomes. Liposomes discussed earlier in the article, are essentially man-made phospholipid bilayers. This forms the carrying barrier between the outer region of the QDBC and the drug space, or in our model, the DS. This is where the compound chemotherapy drugs would be located to neutralize the cancerous cell.
The DS we think to conjugate at about a 12-nanometer thickness starting from the 2 nm quantum dot outwards to the hydrophilic portion of the liposome. This is considering turgor pressure of the bioconjugate which essentially describes the pressure put on the cell walls by the contents of the cell but in this case, the contents of the QDBC.
The liposome itself would be about 4 nm in thickness as this is the thickness of the cellular membranes of the lymphatic cells we are targeting. This thickness was selected because of the fact that osmotic pressure would more effectively absorb the QDBC if the thicknesses of the mediums were similar (4 nm).
There would also be a form of amphiphilic polymer surrounding the quantum dot itself to start building onto it and construct the bioconjugation, while also protecting the quantum dot from the enzymes of the cell’s cytoplasm while also protecting the body from potential heavy metal fallout. This way, when the quantum dot is utilized for sub-cellular labeling, it can remain intact for bioimaging and tracking of the leukemic cells.
Antibodies are proteins that the body’s immune system produces to detect and later on destroy foreign bodies within the system. Within our QDBC, the antibodies would be conjugated upon the same layer as the amphiphilic layer of the liposome as well as on top of the amphiphilic membrane around the quantum dot. This (the antibodies on the outer liposome) would serve the purpose specifically of making sure the QDBC is not attacked by the immune system or any other defense mechanism that the body would have. Should the antibody conjugation be left out, the immune system would detect not particularly the quantum dot, but more so the biological components of the QDBC as they are organic and foreign, leading to an immune response. Adding antibodies to this system would provide protection for the bioconjugate and allow it to perform its functions and get into the cell.
Conjugating antibodies around the QD amphiphilic membrane would be beneficial after the drug release when the quantum dot and its outer membrane are exposed and aligned for subcellular imaging. Because there are enzymes in the cell that destroy waste products, it may identify the QDBC as a “waste” and thus try to eat away at it per se. To prevent this, antibodies conjugated around this quantum dot amphiphilic membrane would deter foreign detection proteins and destructive enzymes, protecting the QDBC and leaving it sound for bioimaging.
Nuclear localization sequences (NLS) are sequences or groups of amino acids that in a way “tag” a protein for entrance into the nucleus of the cell. Now, why does this hold importance in a QDBC that is similar in size to the said nucleus? Well, the compound chemotherapy (CC) drugs are only effective particularly by destroying genetic information that the leukemic cells rely on to replicate and thus become cancerous. We think that by developing a nuclear localization sequence that attaches to the molecules of CC, our bioconjugate delivery system would be more effective in the actual delivery of the drugs. By releasing an NLS paired with the CC, the CC will be absorbed through the nuclear membrane and thus the drugs can be fast-acting, and overall more effective.
Compound chemotherapy, or for our sake CC, is the drug system including three drugs that would be included throughout the Apollo Therapeutics treatment. First off, the main three categories for chemotherapy aforementioned in this article include purine analogues, alkylating agents, and corticosteroids. The three drugs we will be utilizing include drugs from two of those groups: purine analogues and alkylating agents. These drugs are fludarabine (“f”), cyclophosphamide (“c”), and rituximab (“r”).
The “f” and “c” are purine analogues and alkylating agents respectively, both of which negatively impact the genetic components of leukemic cells. Fludarabine works by inhibiting the synthesis of DNA that prevents genetic replication, stunting the growth of cancerous cells. In unison with cyclophosphamide, an alkylating agent which prevents DNA pairing by adding an alkyl group to the guanine base of DNA, these drugs can neutralize a cancerous lymphocyte cell. This CC would belong within the DS (drug space) of the QD bioconjugate. They would each be bound to NLS which would directly transmit these drugs to the nucleus of the cancerous cell. This would provide direct access to the genetic material the drugs are meant to destroy, and therefore would make treatment fast-acting. This CC would essentially render the cancerous cells useless and cell death would occur soon after, treating CLL much more effectively.
Rituximab is a monoclonal antibody used for antibody therapy and is essentially more of a booster for immune fighters towards the cancerous leukemic cells. This would not be a directly delivered drug by the QDBC, but this antibody is definitely worth integrating for treatment to provide patients with even more strength while still getting the chemotherapeutic nano-treatment. This would most likely be administered via an injection after the QDBC solution is intravenously administered.
Apollo Therapeutics & QDBC Drug Delivery System
Now in understanding all the parts of the QDBC DDS, we can better picture how exactly the system would function altogether. Here is a schematic of the process:
The process of Apollo Therapeutics’s delivery system includes 5 main steps of the actual direct delivery:
- The quantum dot bioconjugate (using targeting ligands of ZAP-70 and CD-38 proteins) identifies and attaches to the receptors of cancerous lymphocytes.
- The QDBC then enters the cell where the surrounding liposome is lysed by the enzymes of the cell.
- The CC is released, and using nuclear localization sequences…
- The CC enters the nucleus where the cancer cell is neutralized.
- The remaining quantum dot attaches itself to a sub-cellular labeling platform to monitor the progress of treatment.
In order for the QDBC to even make it into the body, however many conjugates necessary would be suspended in a saline solution and intravenously administered to the patient. Once it gets there, the process from above would ensue.
In order to monitor the progress of treatment, x-ray and MRI systems would scan the patient periodically and because the quantum dots (before conjugated) would have been irradiated with ultraviolet light, the photons would remain intact due to the photo-optic properties of QDs and show up on the scans. This would give status updates to oncologists on what the status of the treatment and the cancer is like.
Overall, this process shows high potential in the field of leukemic treatment and improved benefits in treating this cancer than generalized intravenous chemotherapy. With all of the components provided earlier in this section, this drug delivery system mostly fits the criteria we set earlier on in the article including needing a high drug load capacity, having high encapsulation efficiency, and low toxicity.
However, there are still multiple roadblocks that make this solution nonviable in the present time. Regardless, measures can be put into place to get past those roadblocks in the future.
Complex Ideas Have Complex Obstacles
What you might have gotten from this article is that, yes, it’s very complex. Any technology with a complex structure like this is bound to have multiple challenges to work around.
Obstacle #1: the QDs have a chance of interfering with the immune system when entering the body
How Apollo Therapeutics will work to eradicate this problem: we plan on lacing an antibody layer around the liposome and the QD itself that will prevent attacks from the body’s immune system. The antibody in question is dependent on the patient’s immune state and possible allergies.
Obstacle #2: QD fall out and toxicity in the body
How Apollo Therapeutics will work to eradicate this problem: QDs will not be inserted in large enough amounts to cause any harm to the patient and they will be covered in layers to prevent any toxic fallout from spread throughout the body.
Obstacle #3: in vivo instability — QDs have a chance of running into other bodily structures that the QD should not be interacting with
How Apollo Therapeutics will work to eradicate this problem: we will ensure that the amphiphilic polymers are bound tightly to each other and tight enough to withstand the turgor pressure that the QD will undergo
Problem #4: biological components needed to produce the QDBC are hard to find and synthesize
How Apollo Therapeutics will work to eradicate this problem: the proteins will first be isolated and then prepared to be put together in the QDBC via in vitro
As a moonshot startup, we acknowledge these are not perfect solutions, nor do we know if solutions will work 100%. These solutions were formulated using research and knowledge of chemotherapy, cancer, modern cancer treatment, and the overall functions of the human body.
These questions will be one of the highest priorities once clinical trials, research, and development begin.
Apollo Therapeutics Finances
Determining the cost of the treatment provided by Apollo Therapeutics can vary greatly depending on the patient. As mentioned earlier, regular chemotherapy relies on taking into account the state of cancer, the patient’s general state of health, the patient’s ability to cope with the side effects, and any previous medical conditions or previous cancer treatments. Similarly, our treatments will rely on each patient and will be as personalized as possible to ensure effectiveness.
The cost of treatment from Apollo Therapeutics is dependent on:
- Drug dosage inside each quantum dot
- Duration of the treatment
- What kinds of drugs needed for the treatment
- Number of QDs required
- Material costs
While we can’t say the exact cost of treatment, we can break down some of the individual costs that would go into the actual Apollo Therapeutics therapy process.
First, let’s understand the price of regular chemotherapy. In the past, the average monthly price of chemotherapy in the United States can range from $1,000 to $12,000. Even with coinsurance of around 25%, a patient has to pay $2,500 a month for chemo. To some, this isn’t a lot but to give you some perspective, the average American has a monthly income of $3,600. This means that, even with insurance, almost 70% of the patient’s income is spent on making sure their body can fight cancer inside of them.
What we can grasp from these numbers is that chemotherapy is crazy-expensive.
Most of this cost comes from the high prices of the drugs used in chemotherapy and then the materials costs that go into the manufacturing of the QDs themselves. Going back to the FCR combination we discussed earlier, one dose of each drug will add up to a total of almost $500. Longer treatments will result in the cost building up more. An average cost for 4 chemo sessions can cost up to $48,000. Of course, this cost is over a period of a couple of months. The number of doses is dependent on the patient alone.
In the past, a gram of QDs cost an average of $2,000 to produce. The main reason for the high cost is that the production of QDs requires solvents such as octadecene (ODE) and these solvent accounts for around 90% of production costs. Note that we said “in the past” because now, new research methods are rising that can avoid using ODEs. A new study at MIT started using heat-transfer fluids, like Dowtherm A, in the processing units during production and this has the potential to cut expenses by 80%. Doing that would mean that the same gram that costs over $2,000 to produce will only cost $400 using this new production method.
Given what we know about the uncertainties when it comes to the cost of cancer treatment, it’s hard to determine the exact profit Apollo Therapeutics would be making. We are looking to market to registered hospitals and governments. This technology has the potential to eradicate the threat of leukemia for good and we at ApolloQD want to make sure more people have access to more effective chemotherapy.
Once Apollo Therapeutics is fully established, we are aiming for a 30% profit margin. In many cases of cancer, late diagnoses are very common. People with CLL and leukemia particularly can go months or years without symptoms or even noticing something is wrong. By the time the patient is diagnosed with CLL or other forms of leukemia, it is common that the patient will be entering dangerous stages of cancer. Following this, we can come to the conclusion that they will require more aggressive treatment.
Of course, we understand that Apollo Therapeutics will take some time to become adequately established. Thankfully, we know exactly where to take Apollo in the future.
Our Impact — Apollo and Sustainable Development Goals
When it comes to any entrepreneurial venture that leverages developing technologies to solve global problems, it is highly important that goals are established that can be used to define “success” on a more societal scale. With this in mind, Apollo Therapeutics as a moonshot project aims to follow up with the United Nations’ Sustainable Development Goals in areas including good health and wellbeing, industry, innovation, and infrastructure, and otherwise the social aspect of biotechnologies.
As far as good health and wellbeing, by utilizing the hypothesized bioconjugation of quantum dots for targeted drug delivery, leukemia which is a very pressing form of cancer can be better and more efficaciously treated. This of course targets the SDG of good health and well-being as individuals with this terrible disease would be better able to be treated. Not only that, but those who are being treated with chemotherapy already can have an improved way of life given that a targeted delivery system of oncological medications can prevent the very harmful side effects that are characteristic of the chemo itself.
With Apollo Therapeutics, industry, innovation, and infrastructure are all being targeted. Innovating such a composite of both nanotech and biotech can aid in the development of not only both of those industries but new intersectionality in the medical field. This intersection can pave the way for other extensions of the quantum dot delivery technology for such things as vaccinations, treating hormone imbalances, and other such problems. A biomedical infrastructure can be better built should this technology be further developed.
Flashforward — Apollo Therapeutics in Fifteen Years
Understanding the complexities that are involved in developing Apollo Therapeutics nanotechnologies, it’s going to be at least over a decade or so until Apollo Therapeutics is ready for action.
For the next 5 to 8 years, we plan to carry out research, clinical treatments, and development here in North America. Our team originally being in North America and having the technological advancements available here, the infrastructure for further technological advancements are already in place for Apollo Therapeutics’s future.
After the technology is completely developed, we plan to implement systems of treatment in other countries such as Cyprus, Colombia, and Ethiopia. These countries, among others, were selected because of their high death rate due to leukemia. Additionally, these countries tend to have a larger disparity in their cancer treatment systems. Our treatment is much cheaper than modern chemotherapy. Much of the United States’ hospital profit is from cancer treatment, making American hospitals slightly more hesitant to adopt our technology. Yet, these countries with poor health care would much prefer cheaper and more effective means of saving their populations.
To be realistic in measuring success, we looked at a study done at MIT where researchers used QDs to deliver vaccines and were able to obtain success rates of 92% and 97%. Given that our technology is a little more intricate than the technology used in the study, Apollo Therapeutics aims for a 90% success rate in Phase 2 which is estimated to increase as more research, clinical trials, and development is done in Phase 3.
Given our target success rate, we estimate to reach and help treat 7,000 patients across our Phase 2 Locations. This number was a result of calculating the 90% of each country’s annual leukemia cases.
It will not solve all our problems right away but while we’re expanding our technology to different countries that need it, we will be doing more clinical trials, research, and further development back home. With this work being done, we hope to be able to start targeting other leukemias and soon, other cancers altogether. Apollo Therapeutics is the next step towards a cancer-free world.
We know Apollo Therapeutics cannot cure cancer right away. But our goal is to start decreasing the rates of leukemia-related deaths.
In the end, we will be treating leukemia as if it was as threatening as the flu or the common cold.
