Tumor cells are elusive; they camouflage themselves among the rest of healthy cells and become immortal to survive and proliferate. Despite this, the difficult thing about treating cancer is not killing the malignant cells themselves; there are many toxins that can do it. What makes this battle so tough is overcoming the devastating side effects that treatments like chemotherapy cause in patients.
Therefore, being able to eliminate tumor cells from the inside , without damaging the rest of the healthy tissues of the body, is a true revolution in treatments, which could save many lives. And that is precisely what a team of scientists from the University of Granada (UGR), the Institute of Nanoscience of Aragon (INA) of the University of Zaragoza and the Cancer Research UK Edinburgh Center, at the University of Edinburgh has achieved.
We have been witnessing the appearance of alternative cancer treatments to chemotherapy for years, such as immunotherapy, (which is capable of activating the body’s own immune system to identify and destroy tumor cells), all with the aim of alleviating the aggressive consequences for the health of a chemo or radio treatment. Now, this team of researchers has found a way to deliver these toxic chemicals directly to the correct cells, the tumor cells, leaving the rest of the healthy cells in the body intact. How did they do it?
A molecular Trojan horse
According to a summary of the work, published yesterday by the journal Nature Catalysis , the process would be equivalent to letting a kind of Trojan horse enter the tumor cell. Cancer cells will unexpectedly let exosomes with an effective enemy inside them. Exosomes are biomarkers that most cells secrete, and they are composed of a membrane that contains the characteristics of the cell from which they come. With this membrane, as a disguise, these exosomes, which measure 100 nanometers, would be introduced inside the cancer cell.
The weapon they have inside is a Palladium catalyst. Catalysts serve to accelerate chemical processes. Once inside the tumor cell, the catalyst will transform a toxic molecule until then inactive (panobinostat, a chemotherapy approved in 2015) into active. Now, the Trojan horse has released the anticancer, and the tumor cell has died without implying toxicity to the rest of the tissues.
“We have introduced the catalyst into tiny vesicles or exosomes with a size of the order of 100 nanometers, which are capable of traveling inside the tumor cell. Once there, they have catalyzed a reaction that transforms a passive molecule into a potent anticancer “, points out Jesús Santamaría, professor at the University of Zaragoza , who together with Prof. Unciti-Broceta has led this work published by the prestigious scientific journal Nature Catalysis .
Tumor cell with actin filaments marked in turquoise, the nucleus in blue and the exosomes in green.
This sophisticated molecular process is nonetheless based on everyday life, as the researchers point out: “We use catalysts in many aspects of everyday life because they enable chemical reactions that would not be possible otherwise. For example, the gases that come out of our car go through a catalyst to convert them into others that are less harmful to the environment and health ”. So why hasn’t this process been considered as an anticancer therapy until now? According to the authors: “There are great obstacles: finding suitable catalysts and reactions and, above all, bringing the catalysts into target cells, and not into others.”
In the study “exosomes Cancer-derived loaded With ultrathin palladium nanosheets for targeted bioorthogonal Catalysis” participate Maria Sancho, Victor Sebastian and Manuel Arruebo, University of Zaragoza, and Pilar Martin-Duque, the Agency Aragonesa Foundation for Research and Development (ARAID awarded to the IACS) of the Government of Aragon at the INA and associated with the IIS-Aragon, as well as the UGR researcher, Belén Rubio Ruiz. The work has been carried out in collaboration with the research group of the University of Edinburgh, led by Professor Unciti-Broceta.
Reference:
‘Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis’. Nature Catalysis 2019 DOI: 10.1038 / s41929-019-0333-4
