For those interested, we are happy to propose an article that appeared on the website of the Italian Advanced Therapy Observatory and that we consider very interesting, because it explores a new approach to reduce the side effects of chemotherapy, a very invasive therapy. This ingenious strategy is based on cellulose filaments placed at the end of nanocrystals to capture the excess of chemotherapy drugs. Test results are surprising.
Chemotherapy is still considered the best option for most cancers. However, these drugs cause serious side effects, which reduce the quality of life of patients. A US research team has developed a new nanomaterial for capturing locally administered chemotherapeutics before they enter into the systemic circulation. This strategy is based on a particular form of cellulose nanocrystals, developed to capture the largest number of drug molecules, without side effects on other cells. This approach up to 3200% more effictive than other possible approaches. The results are published in the scientific journal “Materials Today Chemistry”.
Several cancer patients are now starting to benefit from new molecular targeted therapies – the so- called “targeted” drugs, as they specifically block the molecular mechanisms that fuel tumor growth, or from innovative CAR-T cell therapies, based on immune cells “trained” to target cancer cells. However, for decades, chemotherapy, along with radiotherapy and surgery, have been the only possible options, and unfortunately, for many types of cancer, they still are.
Chemotherapy works in a completely different way than the new targeted and personalized therapies: it interferes with the ability of cancer cells to replicate and proliferate quickly. For this reason, it can cause serious side effects, as it also damages healthy tissues that are also made of fast- growing cells, such as hair, skin, and intestinal walls. The main ones are anemia, fatigue, nausea, vomiting, hair loss, cognitive problems, and cardiotoxicity.
Targeted therapies are generally more bearable for patients, but they can only be administered for certain types of cancers. Therefore, on one hand, researchers are studying the molecular mechanisms of cancer to increase the effectiveness of molecular targeted drugs; on the other hand, new strategies are continuously being tested to reduce the side effects of chemotherapy.
CATCHING EXCEEDING CHEMOTHERAPEUTICS
Doxorubicin, for example, is one of the most widely used drugs for liver cancer, but high doses can cause cardiotoxicity. A lower dosage reduces the risk for the patient, but it is also less effective against cancer. A solution may be to administer chemotherapy in high doses locally within the tumor. Even so, some of the drug can reach the systemic circulation and damage healthy tissue. Local administration may work in combination with excess chemotherapy capturing methods.
Since 2014, chemotherapy filters (Chemo-Filters) have been developed, based on the properties of ion exchangers, such as resins. Since most drugs are positively charged, they can interact with a matrix made up of opposite charged polymers. For example, one of the latest systems is based on the ability of drugs such as doxorubicin to bind to the DNA of cancer cells to block replication. In a 2018 study, the negatively charged genomic DNA-coated magnetic nanoparticle system removed up to 98% of doxorubicin from human serum in 10 minutes. However, the removal capacity of these methods is in the order of a few micrograms of drug per milligrams of adsorbent substance.
“HAIRY” CELLULOSE NANOCRYSTALS
A US research team has designed a method based on cellulose nanocrystals that is up to 3200% more effective than other approaches used so far, including the one based on DNA. Researchers have chosen cellulose, the main component of the cell wall of plants, because it is a biocompatible, non-cytotoxic and non-biodegradable material. In particular, they created an engineered version of cellulose, the so-called “hairy” cellulose. Nanocrystals are rod-shaped, with a disordered “tuft” of negatively charged cellulose chains at the end, capable of capturing many molecules of doxorubicin at a time. The name has been chosen because the cellulose chains at the end look like a a tuft of hair
The nanocrystals keep their negative charge stable even in the bloodstream, where many other nanoparticles lose their functionality when they get in contact with proteins and ions in the blood. Researchers have been testing the different possibilities for capturing doxorubicin in various solutions, including human serum. The results were surprising, at least two to three orders of magnitude higher than those of the other available strategies: up to 6000 micrograms of doxorubicin removed per milligram of cellulose nanocrystals.
Experiments also showed that nanocrystals in vitro have no side effects on red blood cells or cell growth and metabolism. Actually, their presence in the culture medium protects cells from the harmful effects of treatment with doxorubicin. Amir Sheiki, a biomedical engineer at Penn State University and coordinator of the study, commented on the possible applications of this system: “Nanocrystals could capture excess drugs exiting the inferior vena cava of the liver. Doctors could give higher doses of chemotherapy to fight cancer faster without harming healthy cells. Once the treatment is finished, the device could be removed “.
Also, according to Sheiki, the use of “hairy” cellulose nanocrystals could also have other applications outside the world of medicine. His team recently designed nanocrystals that can selectively bind to neodymium, a rare earth metal, to catch this precious material from electronic waste.