28 September 2020

Trojan Nanocon

A research team from Nanyang Technological University, Singapore, has created a nanoparticle with the properties of a "Trojan horse" by coating it with L-phenylalanine , a specific amino acid, along with other amino acids necessary for the survival and growth of cancer cells. L-Phenylalanine is known as an essential amino acid because it cannot be produced by the body and must come from food, usually meat and dairy products.

Studies by other groups have shown that tumor growth can be slowed down or prevented by blocking cancer cells' access to amino acids. Scientists believe that depriving cancer cells of amino acids, for example, by fasting or a special diet with a lack of protein, can be an effective way to treat cancer.

However, such strict dietary restrictions are not suitable for all patients, especially those who are at risk or suffer from cachexia, a condition resulting from a long–term chronic disease that causes weight loss and muscle mass. In addition, for many patients, compliance with the diet is a very difficult task.

In an effort to exploit the amino acid dependence of cancer cells, but to avoid the problems associated with strict dietary restrictions, Singapore researchers have developed an alternative approach. They took an FDA-approved silicon dioxide nanoparticle as a basis and coated it with L-phenylalanine. The researchers found that in tests on mice, it effectively and very specifically killed cancer cells, causing them to self-destruct.

Anti-cancer therapeutic nanoparticles have ultra-small dimensions (diameter of 30 nanometers). They were called Nanoscopic phenylalanine Amino Acid Mimic (Nanoscopic phenylalanine Porous Amino Acid Mimic, Nano-pPAAM).

The peculiarity of the work is that the new approach consisted in using the nanomaterial as a medicine, and not as its carrier. The properties of Nano-pPAAM are internal and should not be "activated" by any external stimuli. Thus, the amino acid L-phenylalanine acts as a "Trojan horse" – a disguise hiding a therapeutic drug inside.

Therapeutic properties of Nano-pPAAM

As proof of concept, scientists tested the effectiveness of Nano-pPAAM in vitro and in mice and found that nanoparticles led to the death of about 80% of breast cancer, skin cancer and stomach cancer cells, which is comparable to the effect of a standard chemotherapeutic drug, for example, cisplatin. Tumor growth in mice with human triple negative breast cancer cells was also significantly slower compared to control models.

The amino acid coating Nano-pPAAM helps the nanoparticle to penetrate cancer cells together with the amino acid carrier protein LAT1. Once inside cancer cells, Nano-pPAAM stimulates the production of an excessive amount of reactive oxygen species, causing the self-destruction of cancer cells and remaining harmless to healthy cells.

The new strategy does not involve the use of any pharmacological drugs, therefore it is not associated with the development of drug resistance. It relies on the unique ability of nanoparticles to release reactive oxygen species to destroy cancer cells. That is why Nano-pPAAM can be a salvation for cancer patients who do not respond to traditional treatment.

Currently, the authors are working on further improving the Nano-pPAAM design in order to make the method more accurate in targeting certain types of cancer and achieve higher efficiency, including by combining the method with other types of treatment, for example, immunotherapy.

Article by Z.Wu et al. Potential By Design: Amino Acids Mimicking Porous Nanotherapeutics with Intrinsic Anticancer Targeting Properties published in the journal Small.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Nanyang Technological University: NTU Singapore scientists develop a 'Trojan horse' approach to kill cancer cells without using drugs.

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