Researchers from the Tokyo University of Science have successfully modified mesenchymal stem cells (MSCs) for the targeted delivery of large amounts of anti-cancer drugs to developing tumor cells.
The number of cancer patients is increasing every year around the world. In this regard, the search for effective methods of therapy is one of the most difficult and constant tasks in modern medicine. Besides drug development, drug delivery to target organs is also a major challenge facing the cancer research community.
Many scientific groups have tried to develop methods for effectively delivering anti-cancer drugs to tumors. Up to now, a promising approach is the use of mesenchymal stem cells (MSCs), which have a special ability to find oncological formations and migrate to them (the effect of “homing”). This means that it is theoretically possible to load anticancer drugs into “tumor-homing” MSCs and use them to prevent cancer progression.
However, pilot studies show that MSCs have limited capacity to load anticancer drugs and, as a rule, after loading drugs, they lose their ability to target and reach tumor cells.
In a recent study published in the Journal of Controlled Release, Japanese scientists led by Dr. Kosuke Kusamori and Professor Makiya Nishikawa from Tokyo University of Science tried to find methods for modifying MSCs that could get around these problems.
Dr. Kusamori, Assistant Professor in the University’s Department of Pharmacy says, “We wondered if the answer to our dilemma of modifying mesenchymal stem cells with an anticancer drug was to exploit the property of mesenchymal stem cells to accumulate in tumor tissues”.
Using the well-known avidin-biotin complex method (ABC method), the researchers used liposomes, cellular lipid vesicles widely used as drug delivery systems, to transfer the anti-cancer drug doxorubicin (DOX) to the surface of mouse MSCs. They called the lipid vesicles that carry DOX “DOX-Lips”.
The researchers found that DOX-Lips loaded MSCs could carry the drug and selectively target mouse colon cancer cells growing in artificial cultures in the laboratory. These modified MSCs can not only carry a significant amount of drug but also efficiently deliver it to target cancer cells.
To test the reproducibility of this function in a living system, the scientists used models of mice with skin and lung cancer. They found that in both cases, DOX-Lips were able to efficiently reach cancer cells and release drugs into their cytoplasm. The researchers concluded that modified MSCs could completely suppress tumor growth in mouse models.
This new method has several advantages. Firstly, the process takes less time compared to previously known methods.
As noted by Yukiya Takayama, a doctoral student in Professor Nishikawa’s lab and co-author of the study, “The relatively short duration of the ABC method made it possible to quickly modify the cell surface with DOX-Lips and avoid cell damage”.
Secondly, this method did not affect the attachment of MSCs to cancer cells, thereby ensuring the maximum efficiency of drug delivery. Third, contrary to previous claims that only certain sizes of liposomes can be used to deliver drugs, new research suggests that the size of the lipid vesicles likely does not affect drug delivery. This discovery can also be used to deliver many different doses of drugs.
Thus, the combination of ABC and Lips appears to be the answer to the researchers’ dilemma. Professor Nishikawa is very pleased with the results.
“We have succeeded in developing a new targeted cancer therapy”, – he observes. “Mesenchymal stem cells can migrate to brain tumors and minute cancer lesions that are otherwise inaccessible to conventional drug delivery systems. Our method may thus be effective against intractable cancers”.
Thus, this study represents a promising advance in the field of cancer research. The new method may be the answer to the question of how to deliver the drug directly to the tumor.