Scientists identify new target to deliver anti-cancer drugs to tumor cells

The evolution of human beings simultaneously corresponds with the evolution of cancer, and as a result, the quest for identifying efficient treatment techniques for cancer patients has remained constant and challenging.

The Bull’s Eye: New Modified Stem Cells Can Deliver Drugs Specifically to Tumor Cells

As humans evolve, cancer also evolves in parallel, making the race for finding efficient treatment methods for cancer patients challenging and constant. In addition to designing drugs for treatment, the delivery of these drugs to targeted organs is also a major challenge faced by the cancer research community. Video Credit: Tokyo University of Science.

Apart from developing medications for treatment, the delivery of such medications to organs of interest also poses a considerable challenge to the cancer research community.

In this regard, several research teams have attempted to design methods to efficiently transport anti-cancer medications to tumors. A fascinating technique makes use of distinct cell groups in the human body, called mesenchymal stem cells (MSCs). These cells have a unique potential to detect and migrate toward tumors.

This implies that at the theoretical level, these “tumor-homing” MSCs can be loaded with anti-cancer medications and can be used to block the progression of cancer. But pilot studies have demonstrated that MSCs have only limited anti-cancer drug loading capacity, and they are likely to lose their potential to target and reach the cancer cells following the loading of drugs.

In a new study, Japanese researchers, headed by Dr. Kosuke Kusamori and Professor Makiya Nishikawa from Tokyo University of Science, set out to identify a new method to alter the MSCs to overcome these issues. The study was published in the Journal of Controlled Release.

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.”

Dr Kosuke Kusamori, Assistant Professor, Department of Pharmacy, Tokyo University of Science

With the help of the popular “avidin-biotin complex” (ABC) technique, the team used liposomes—cellular lipid bags often utilized as drug delivery systems—to carry the doxorubicin (DOX) anti-cancer drug to the surface of certain MSCs in mouse models. The researchers dubbed these DOX-carrying lipid bags “DOX-Lips.”

The team observed that the MSCs loaded with DOX-Lips are capable of carrying and selectively targeting the colon cancer cells in the mouse; these cancer cells were being grown in artificial cultures in the laboratory. Such altered MSCs could carry a considerable proportion of the medication and can also efficiently transport it within the target tumor cells.

To find out if this aspect is simulated in a living system, the researchers employed a mouse model that had both lung and skin cancers. They observed that in both cases, DOX-Lips efficiently reached the tumor cells and discharged the medication within the cytoplasm of the tumor cells. The team concluded that the altered MSCs could fully inhibit the growth of cancer in mouse models.

The new technique offers a number of benefits. Firstly, the procedure is much faster than the formerly known technique. As Yukiya Takayama, the co-author of the study and a doctoral student in Professor Nishikawa’s laboratory, observed, “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, the new technique did not impact the process of cell attachment to tumor cells, thus assuring the highest efficiency in drug delivery.

Thirdly, in contrast to earlier observations that only a specific size of lipid bags can be used to deliver the medications, the latest research work indicates that the size of the lipid bags is highly likely to impact drug delivery; this discovery can also be manipulated to transport several different doses of medications.

Therefore, the ABC technique combined with the use of DOX-Lips appears to be the solution to the investigators’ dilemma. Professor Nishikawa is indeed happy about these outcomes.

We have succeeded in developing a new targeted cancer therapy. 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.”

Makiya Nishikawa, Professor, Tokyo University of Science

Therefore, the new study represents a promising development in the area of cancer research—the novel technique developed by the team could well be the solution on how to deliver the treating medication to cancer’s doorstep.

Source:
Journal reference:

Takayama, Y., et al. (2020) Anticancer drug-loaded mesenchymal stem cells for targeted cancer therapy. Journal of Controlled Release. doi.org/10.1016/j.jconrel.2020.10.037.

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