02 December 2019

Pills in a cage

Bone marrow will become a component of a cancer drug

Maria Nedyuk, Izvestia

For the first time, Russian researchers have managed to use stem cells for targeted delivery of cancer drugs. Their use for the treatment of cancer has caused scientists concerns, as they are able to stimulate the growth of tumors. However, it turned out that this does not always happen. Specialists take the patient's bone marrow cells and load them with special capsules containing a toxic substance. Getting into cancer-affected tissues, the capsule under the influence of a laser releases a toxin that kills both the cell itself and the tumor. Such therapy has already shown its effectiveness in the melanoma model.

Cellular Courier

In modern oncomedicine, there is an acute problem: the effectiveness of most drugs depends on the dose of antitumor drug administered – the higher it is, the more effective the therapy. However, sooner or later there comes a limit when the effect of the drug is not yet effective enough, and the dosage used approaches a critical point and becomes toxic to the body as a whole. To overcome this barrier, it is necessary to use the drug rationally, delivering it directly to the focus of the disease.

In addition, with the standard approach, a large dose of the injected toxic antitumor drug is distributed throughout the body along with the bloodstream. This can create another barrier to drug delivery to the area of interest: tumors are often quite dense formations, which means that blood flow in them is difficult. Thus, with standard administration, an antitumor drug may not always accumulate freely in sufficient quantities in the area of neoplasms.

ITMO University has found a way to deliver the drug in a targeted manner to the tumor area and release it using infrared radiation. As one of the authors of the study, Oleksiy Peltek, a graduate student of the Faculty of Physics and Technology, explained to Izvestia, stem cells were selected as deliverers, which will be taken from the patient's bone marrow.

– These cells are capable of pathotropism, that is, directed migration to the neoplasm focus due to the large accumulation of leukocytes and macrophages there (cells reacting to inflammation. – "Izvestia"), – the scientist explained. – It is clear that migrating stem cells cannot be loaded directly with toxic antitumor drugs, as this can negatively affect their biological functions. Therefore, antitumor drugs must first be isolated and then loaded into stem cells, which is what we have done in our work.

Sense of light

To solve this problem, researchers have developed submicron hollow carriers based on polymers and silicon dioxide – polyelectrolyte capsules (submicrocapsules). After the drugs were placed in the shell, the stem cells were modified and the capsules were loaded inside them.

– The developed capsules are photosensitive, that is, they are capable of being destroyed by infrared radiation and remotely release the drug, – said Oleksiy Peltek.

Photosensitivity allows you to release the drug at the right time and in the right place. Thus, scientists have developed a smart system for delivering antitumor drugs directly to the area of malignant neoplasms. The researchers suggest that the capsules can be injected into the vessels surrounding the tumor.

Studies on cells have shown that it takes three days for the release of microcarriers. After this period, it is proposed to influence the tumor localization area with infrared radiation. Stem cells can also be used to fight metastases. But since it is difficult to find out exactly where they are, the developers suggest using carriers for this purpose that release the drug without irradiation. Their development is already underway.

The effectiveness of targeted delivery of the obtained systems was tested on primary melanoma cells – models of tumor spheroids that were isolated from the tissues of real cancer patients.

Stem cells are able to migrate to tumor foci, as the tumor specifically attracts them with the help of special biologically active substances and makes them work for themselves, supporting growth and metastasis, Albert Rizvanov, director of the Scientific and Clinical Center for Precision and Regenerative Medicine of Kazan Federal University, told Izvestia. However, in this case, scientists managed to "deceive" cancer.

– Packaging drugs in microcapsules, loading such carriers into stem cells and releasing them under the influence of light into tumors really partially solves the problem of targeted delivery. Moreover, in this way, stem cells will deliver their deadly cargo not only to the primary focus, but also to all metastases in the body," the scientist noted.

Vladimir Potemkin, head of the laboratory of computer modeling of medicines at SUSU (the university participating in the 5-100 project), believes that it is too early to talk about the success of such smart delivery systems.

– Development requires clinical trials, which take more than one year. But it is necessary to move in this direction. The main problem of the treatment of tumor diseases is the similarity of healthy and tumor cells," the scientist explained. – Therefore, it will be possible to talk about the effectiveness of the new delivery method only after long-term research.

ITMO scientists also note that, despite the initial successes, in order to implement the developed smart delivery systems into clinical practice, it is necessary to go through a difficult path of preclinical and clinical studies, which require time and financial investments.

The next step of ITMO scientists will be experiments on model animals.

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