A new approach that turns a nanoparticle into a ‘Trojan horse’ that causes cancer cells to self-destruct, a research team at the Nanyang Technological University, Singapore (NTU Singapore) has found.
The researchers created their ‘Trojan horse’ nanoparticle by coating it with a specific amino acid—L-phenylalanine—that cancer cells rely on, along with other similar amino acids, to survive and grow. L-phenylalanine is known as an ‘essential’ amino acid as it cannot be made by the body and must be absorbed from food, typically from meat and dairy products.
Research teams have shown that cancer tumor growth can be slowed or prevented by ‘starving’ cancer cells of amino acids.
ExploitING the amino acid dependency of cancer cells but avoid the challenges of strict dietary regimes, the NTU researchers devised a novel alternative approach.
They took a silica nanoparticle designated as ‘Generally Recognized As Safe’ by the US Food and Drug Administration and coated it with L-phenylalanine, and found that in lab tests with mice it killed cancer cells effectively and very specifically, by causing them to self-destruct.
Their findings, published recently in the scientific journal Small, may hold promise for future design of nano therapies.
The anti-cancer 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 “Nanoscopic phenylalanine Porous Amino Acid Mimic”, or Nano-pPAAM.
Intrinsic anti-cancer therapeutic properties of Nano-pPAAM
As a proof of concept, the scientists tested the efficacy of Nano-pPAAM in the lab and in mice and found that the nanoparticle killed about 80 per cent of breast, skin, and gastric cancer cells, which is comparable to conventional chemotherapeutic drugs like Cisplatin. Tumor growth in mice with human triple negative breast cancer cells was also significantly reduced compared to control models.
Further investigations showed that the amino acid coating of Nano-pPAAM helped the nanoparticle to enter the cancer cells through the amino acid transporter cell LAT1. Once inside the cancer cells, Nano-pPAAM stimulates excessive reactive oxygen species (ROS) production—a type of reactive molecule in the body causing cancer cells to self-destruct while remaining harmless to the healthy cells.
The scientists are 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.