Nucleolin — The Holy Grail of Cancer Treatments?

Photo by National Cancer Institute on Unsplash

June 07, 2014. A day I’ll never forget. Just a few days before, my great grandmother had been diagnosed with a glioblastoma. She was scheduled to have surgery to remove the tumor on this day. The doctor said it will be an easy procedure as the tumor had not spread so far. Little did I know, it was just false hope.

After the surgery, the doctor told us that most of the tumor had been removed, so she should be fine. But no longer than 9 months later, she had died from cancer.

How? What? I thought the cancer was cured. Just like you, these thoughts raced through my head when I heard the news. I soon found out that the surgery was ineffective, as the cancerous cells the surgeons unknowingly left behind had repopulated and spread throughout her body.

While there have been many breakthroughs, there is still no “cure” for this disease, mostly in part because each cancer is unique. However, there may be an unheard way around it…

A Tumor

To understand the solution, you must first understand the problem. This starts with knowing how tumors work, and what nucleolin is (plays a big role in tumor cells).

In the most basic form, tumors are abnormal growths in your body, which can be either benign or malignant. Benign tumors aren’t cancer, but malignant ones are. Benign tumors only grow in one place. They cannot spread or invade other parts of your body. Even so, they can be dangerous if they press on vital organs, such as your brain.

Tumors are made up of extra cells. Normally, cells grow and divide to form new cells as your body needs them. When cells grow old, they die, and new cells take their place. Sometimes, this process goes wrong. New cells form when your body does not need them, and old cells do not die when they should. These extra cells can divide without stopping and may form a tumor.

Nucleolin

So, what is this “miracle” protein?

Nucleolin (NCL) is one of the most abundant non-ribosomal proteins of the nucleolus - where it plays a central role in transcription (copying DNA). NCL is also found outside of the nucleolus, in the nucleoplasm, cytoplasm as well as on the cell membrane.

It acts in all cell compartments to control cellular homeostasis, which balances internal factors to keep a cell healthy, and therefore each cellular group of NCL can play a different role in cancer development. The increased quantity of NCL and its increased gathering at the cell membrane is a common feature of several tumor cells. In cancer cells, NCL overexpression influences cell survival, rapid growth, and invasion through its action on different cellular pathways.

Basically, NCL is only found on the surface of tumor cells. In healthy cells it can only be found mostly in the nucleolus, making it undetectable. This is what makes the solution work.

The Solution

Now that you know the importance of nucleolin, let me give you the rundown of how this can cure cancer.

But before we jump in, there is a key element to making this all work. A DNA aptamer. In essence: it’s a short, single-stranded DNA molecule that can selectively bind to a specific target, including proteins, peptides, carbohydrates, small molecules, toxins, and even live cells. Using this, the aptamer can be altered to only bind to the protein nucleolin. This will allow it to easily “hunt” the NCL down while in the bloodstream.

Nanobots to the Rescue

We’re almost there. There’s only one thing left to creating the potential cure for cancer. The use of a nanobot.

The idea here is that we can use a nanosized particle to “hold” all the components to fight cancer, and then deliver it to the tumor.

How it works:

  • Each nanorobot is made from a flat, rectangular DNA origami sheet, 90 nanometers by 60 nanometers in size
  • A key blood-clotting enzyme, called thrombin, is attached to the surface. Thrombin can block tumor blood flow by clotting the blood within the vessels that feed tumor growth, causing a sort of tumor mini-heart attack and leading to tumor tissue death
  • After an average of four thrombin molecules are attached to the flat DNA scaffold, the sheet folds in on itself like a sheet of paper into a circle to make a hollow tube
  • Here’s where it all comes together. The key to making it all work is to attach the DNA aptamers to the corners of the sheet. Like I said before, this will allow the nanobot to hone in on the tumor
  • The nanoparticles are then injected into the bloodstream via IV in search of the tumor
  • Once bound to the tumor blood vessel surface, the nanorobot was programmed, like the notorious Trojan horse, to deliver its unsuspecting drug cargo into the very heart of the tumor, exposing the thrombin
  • From there, the nanorobots worked fast, congregating in large numbers to quickly surround the tumor in just hours after injection to cut the blood supply, thus killing the tumor

Progress in the Path

If this is so effective, why isn’t it being used? This is probably the most common thought running through your head right now, and it’s understandable. With any new development, there needs to be a lot of testing to make sure there is no harm to the patient.

In a recent study by a team at ASU, they discovered that the nanorobots were safe and effective in shrinking tumors.

“The nanorobot proved to be safe and immunologically inert for use in normal mice and, also in Bama miniature pigs, showing no detectable changes in normal blood coagulation or cell morphology,” said Yuliang Zhao, one of the main team members working on the project.

Most importantly, there was no evidence of the nanorobots spreading into the brain where they could cause unwanted side effects, such as a stroke. So it’s safe as of right now, but only in small to mid-sized animals.

Furthermore, the treatment blocked tumor blood supply and generated tumor tissue damage within 24 hours while having no effect on healthy tissues. After attacking the tumors, most of the nanorobots were cleared and degraded from the body after 24 hours.

The team also tried their system in a test of a primary mouse lung cancer model, which mimics the human clinical course of lung cancer patients. They showed shrinkage of tumor tissues after a two-week treatment.

Though it is effective in smaller-sized animals, it has yet to be found out whether or not it’s effective in humans. Without further research, this groundbreaking discovery may just disappear in a few months.

Key Points

If you didn’t feel like reading it all, here are some things you can take away:

  • Cancer is a disease that kills millions and there is still no cure for it
  • Common treatments, such as surgery, are ineffective as they can often cause cancer to come back again
  • Nucleolin is a protein in all cells but only occurs in high amounts on the surface of tumor cells
  • Aptamers are single-stranded pieces of DNA that can be modified to target a specific protein, in this case, nucleolin
  • Nanoparticles can be created to hold all the components to target and then kill a tumor cell once injected into the bloodstream
  • Components include thrombin (blood-clotting drug), a flat sheet of DNA, and DNA aptamers
  • This treatment has only been found to be useful in mice and other small-sized animals with cancer
  • Further research will be required to see if it’s effective in humans or not

Thanks for reading, and feel free to email me with any questions or opportunities at akashapatel@gmail.com

Innovator | Thinker | Creator. Passionate about medicine and its nanotechnological implications. Working on executing an idea. Website: akashapatel.com