Research: Killing cancer cells with a 'Trojan horse' approach

By: Amanda Lee, Writer, Communications and Outreach

Cancer is a prevalent problem globally which has no cure. Even with treatments, patients may experience a cancer recurrence in their lifetime.

To address this problem, researchers at NTU Singapore – co-led by LKCMedicine Vice-Dean (Faculty Affairs) Associate Professor Tan Nguan Soon – have developed a 'Trojan horse' approach to trigger cancer cells to self-destruct.

Without using any drugs, they created a 'Trojan horse' nanoparticle by coating it with a specific amino acid, L-phenylalanine, that cancer cells rely on to survive and grow.

L-phenylalanine is an 'essential' amino acid as it cannot be made by the body and must be absorbed from food such as meat and dairy products.

Lead author of the study Assistant Professor Dalton Tay from the School of Materials Sciences and Engineering said, "By removing the drug component, we have effectively simplified the nanomedicine formulation and may overcome the numerous technological hurdles that are hindering the bench-to-bedside translation of drug-based nanomedicine."

(Left to Right) Members of the NTU research team include Assistant Professor Dalton Tay from the School of Materials Science and Engineering, Research associate Kenny Wu and Associate Professor Tan Nguan Soon

In their study, the research team took a nanoparticle made of silica, designated as 'Generally Recognized As Safe' by the US Food and Drug Administration and coated it with L-phenylalanine. Using lab mice, they found that the nanoparticle killed cancer cells effectively and very specifically causing them to self-destruct.

Named the "Nanoscopic phenylalanine Porous Amino Acid Mimic", or Nano-pPAAM, the anticancer therapeutic nanoparticle, which is ultrasmall, has a diameter - 30 nanometres or approximately 30,000 times smaller than a strand of human hair. Their research findings were published recently in the scientific journal, Small.

_{In lab tests, the scientists found that Nano-pPAAM killed about 80 per cent of breast, skin, and gastric cancer cells, which is comparable to conventional chemotherapeutic drugs like Cisplatin}

"Instead of starving the cancer cells of essential amino acid, which may encourage the cancer cells to change their energy source, the nanoparticles are cloaked by an essential amino acid to be taken up by the cancer cells through the 'Trojan horse' strategy. Once internalised, the nanoparticles stimulate high dose of reactive oxygen species (ROS) that conceivably outstripped the antioxidant capacity of the cancer cells, killing them without the need for a drug. This is unlike other studies that just use nanoparticle as a vehicle to deliver drug," said A/Prof Tan.

During their study, the researchers found that the nanoparticle killed about 80 per cent of breast, skin, and gastric cancer cells, which is comparable to conventional chemotherapeutic drugs such as Cisplatin. They also found that tumour growth in mice with human triple negative breast cancer cells was significantly reduced compared to control models.

Further research showed that the amino acids coating of Nano-pPAAM helped the nanoparticle to enter the cancer cells through the amino acid transporter cell LAT1. The mesoporous architecture of the nanoparticles was found to be an important feature for its anticancer properties.

_{The anticancer therapeutic nanoparticle is ultrasmall, with a diameter of 30 nanometres, or approximately 30,000 times smaller than a strand of human hair, and is named Nano-pPAAM}

A/Prof Tan added that with current chemotherapy drug treatment, a common issue faced is that recurrent cancer becomes resistant to the drug. "Our strategy does not involve the use of any pharmacological drugs but relies on the nanoparticles' unique properties to release catastrophic level of ROS to kill cancer cells," he added.

The research team is now looking to further refine the design and chemistry of the Nano-pPAAM to make it more precise in targeting specific cancer types and achieve higher therapeutic efficacy. This includes combining their method with other treatment modalities such as immunotherapy which uses the body's immune system to fight cancer.