The Nano-Infiltrator at Cancer’s Doorstep

The Nano-Infiltrator at Cancer’s Doorstep

Scientists at Universiti Putra Malaysia have designed a new nanoparticle that delivers a chemotherapy drug straight to cancer cells. It tricks the cell into accepting the drug, and like a Trojan Horse, sabotages it from within. This new method is potentially more lethal to cancer cells than conventional intravenous delivery. With this, scientists are one step closer to treating cancer efficiently, minimising damage to the body.

Written By: Micaela Leong

The war rages on. The attacks are indiscriminate: children, elderly, the young and healthy. As they struggle to fight for their lives, many succumb to death, and few live to tell the tale. Meanwhile, scientists in laboratories all over the world are hunched over their microscopes and petri dishes, striving to create a solution that could put all this senseless killing to rest. Welcome to the battlefield of cancer.

The Nano-Infiltrator

Scientists at Universiti Putra Malaysia have joined the fray, and designed a nanoparticle equipped with special components that not only specifically targets colorectal cancer cells, but also tricks it into accepting the drug. It is comprised of four main parts: doxorubicin (DOX), chemotherapy medication; truncated hepatitis B core antigen (tHBcAg), that can self-assemble into extremely tiny carriers; polyacrylic acid (PAA), that releases DOX in low pH environments; and folic acid (FA), that binds to receptors on the cancer cell, triggering it to “open” and accept the drug.

With all parts combined, the nanoparticle acts like a well-trained infiltrator sent into enemy territory, tasked with implanting explosives in enemy headquarters. The Malaysian scientists loaded DOX onto the nanoparticles, and introduced them into simulated physiological conditions of tumour tissue. The FA attached to the nanoparticle acts like an identification key card. Without the card, forced entry is difficult and could trigger an alarm. However, When the key card is swiped through the reader, a person can safely enter. Similarly, DOX could enter the cancer cell by itself, but is inefficient and could be kicked out of the cell. Alternatively, with the use of FA, the nanoparticle can dock onto the cancer cell’s receptors and trigger endocytosis. The cell membrane morphs into a cup-like shape to surround DOX and brings it into the cytoplasm - unknowingly accepting the deadly drug. Once inside, DOX sabotages enzymes in the cell’s DNA replication machinery, halting the cell’s ability divide, and the tumour ceases to grow.

Know Thy Chemistry

Before understanding how this nanoparticle is a potential game changer, first we must understand how cancer cells and existing treatments function. Cancer cells are notoriously hard to kill because of their abnormal ability to uncontrollably grow and divide. Chemotherapy drugs are designed to halt cell division by attacking the cell’s DNA replication process. Like throwing a spanner into the works, DOX binds to one of the key enzymes in DNA replication, preventing replication to continue, inhibiting further growth or cell division.

However, a major problem with chemotherapy medication is its inability to distinguish between cancerous and healthy cells. Since chemotherapy is designed to kill cells that rapidly divide, healthy cells that naturally regenerate frequently, such as intestinal lining, hair, and blood cells, get targeted as well. Even though these tissues can heal and recover, side effects, such as diarrhoea, hair loss, and low blood count, happen in the meantime. Thus, scientists are continuously trying to design new methods and medication that only kill off cancer cells, but leave healthy cells unharmed.

Locked and Loaded

This nanoparticle can prevent collateral damage by functioning only in cancer cell environments. PAA, the molecule that holds DOX inside the carrier, can respond differently depending on pH. PAA is negatively-charged, while DOX is positively-charged, so they are attracted to each other. When exposed to neutral pH in normal healthy tissue, the two remain bonded. However, once they are in the acidic territory of tumour tissue, H+ ions interfere with their attraction, causing PAA to let go of DOX. This means the drug is released in the right place at the right time, instead of attacking all cells haphazardly like a loose cannon.

The nanoparticle also takes advantage of the presence of folate receptors on cancer cells, the receptors that FA binds to. The receptors are overexpressed in cancer cells, meaning cancer cells have abnormally more receptors than healthy ones. With more receptors, it is easier for FA on the nanoparticle to attach to the cancer cells, rather than to attach to normal ones. Compared to DOX on its own, the nanoparticle is not only more lethal on cancerous cells, but healthy tissue also suffered less harm.

Cancer cells also absorb DOX at a slower rate with the nanoparticle, as opposed to free DOX. A slow rate of absorbance may seem contrary to people’s perception of an efficient drug. However, a controlled, regulated release of the drug means its effects are more long-lasting and sustained over time, rather than bombarding the tumour with chemotherapy drugs. A more sustained effect also translates to fewer doses for the patient and minimal discomfort.

Victory on the Horizon

Even though this nanoparticle offers great hope and has great potential, the effects on humans is still unknown and untested. Like any new treatment, it needs to go through multiple rounds of clinical testing, which is why developing a panacea for cancer is a long and arduous process. Despite this, the Malaysian scientists’ innovative design of a safer and more effective drug delivery system, opens doors to the possibility of better treatment, and provides greater understanding of how to address current problems.

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References

Biabanikhankahdani, R., Alitheen, N. B., Ho, K. L., & Tan, W. S. (2016, November 24). PH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery. Retrieved April 03, 2017, from http://www.nature.com/articles/srep37891

Doxorubicin. (n. d.). Retrieved April 03, 2017, from http://chemocare.com/chemotherapy/drug-info/doxorubicin.aspx

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Second written assignment for SP 1541: Exploring Science Communication Through Popular Science.