MIPT scientists have developed nanoparticles for the treatment and diagnosis of cancer

MIPT scientists have developed nanoparticles for the treatment and diagnosis of cancer

Picture. Structures of multimodal targosomes for oncoteracy. Source: Journal of Controlled Release

Researchers of the Institute of Biophysics of the Future of Moscow State University have developed an innovative class of nanoparticles – targosomes – for the therapy and diagnosis of cancer. Nanoparticles have undergone laboratory tests on rodents. The tumor destruction efficiency was more than 90%. The results of the study were published in the highly rated scientific publication Journal of Controlled Release.

Cancer is currently one of the leading causes of death worldwide, and although significant progress has been made in the development of new treatments, surgery and/or chemotherapy continue to be the primary treatment strategies. A significant drawback of chemotherapy is the non-specificity of this method. A large amount of a low-molecular-weight toxic compound enters the patient’s body systemically, which damages not only cancerous cells, but also normal cells. This leads to serious side effects (nausea, vomiting, indigestion) associated with hepatotoxicity, renal toxicity, cardiotoxicity and other undesirable effects.

The task of modern science includes the development of anticancer compounds that would be not only cytotoxic to cancer cells, but also devoid of the disadvantages of systemic methods of administration. A lot of work is being done in the field of development of compounds that implement the concept of targeted delivery to certain types of cells, for example, due to specific interactions with tumor markers – receptors on the surface of cancer cells.

The most promising platform for the creation of targeted oncotherapy agents are nanostructures of various nature, especially polymeric ones based on a copolymer of lactic and glycolic acids (PLGA), due to their exceptional biocompatibility and complete biodegradability. Such nanostructures can be loaded as containers with the widest range of compounds of different nature, and their surface is equipped with recognition elements for targeted delivery to target cells.

But any oncotherapy is complicated by the fact that cancer cells have a strong variability and a high mutation rate, which allows them to quite easily acquire resistance to various methods of exposure. This stimulates pharmaceuticals to create systems that have a complex of different mechanisms of cytotoxicity, in order to achieve the maximum effect.

In order to solve these complex tasks, scientists of MIPT have developed a universal nanoplatform – targosomes. These are the first targeted nanocarriers based on a copolymer of lactic and glycolic acids for the diagnosis and chemophototherapy of highly aggressive HER2-overexpressing tumors. HER2 is a membrane protein of the human epidermal growth factor receptor family that is frequently overexpressed in breast cancer. It is associated with a high metastatic potential of the tumor, a high risk of recurrence and low patient survival.

“We have done extensive research and experimental work. As a result, the successful visualization of the tumor and distant metastases was demonstrated using the example of targosomes loaded simultaneously with a fluorescent dye for diagnosis, a photosensitizer, and a chemopreparation. They were focused on the clinically relevant tumor marker HER2. The tumor destruction efficiency was more than 90%.

“It was the combined effect of various mechanisms of cytotoxicity: a chemotherapeutic drug, irinotecan and a photosensitizer when an external source of IR radiation was connected — that made it possible to achieve such a high therapeutic efficiency in the treatment of tumors in laboratory rodents,” she said about the project. FTI.

This method combines several functions on one nanoplatform. Encapsulation of the drug in nanoparticles improves its effect and absorption by the body, while reducing systemic toxicity. In addition, modification of the surface of nanoparticles with target molecules ensures precise targeted delivery of drugs and their improved distribution throughout the body. Nanoparticles based on the PLGA polymer are characterized by a high efficiency of drug encapsulation. A number of drugs based on it have already been approved in the USA for therapeutic and diagnostic use.

The nanoparticles demonstrated a 7-fold increase in binding and an almost 18-fold increase in cytotoxicity for cells overexpressing HER2 compared to cells lacking HER2 expression. This enhancement of cytotoxicity under the influence of infrared radiation increased more than 20 times. In vivo studies have demonstrated the effectiveness of the nanoparticles for imaging primary tumor sites and metastases and demonstrated tumor growth inhibition of 93%, making these nanoparticles excellent candidates for translation into therapeutic applications.

“Multimodal biocompatible targosomes are drugs of the medicine of the future, as they can be adjusted to the individual characteristics of each patient. This is a real basis for the development of personalized medicine drugs. A unique combination of chemotherapy, diagnostic and phototherapeutic properties in one targeted platform will allow to achieve high efficiency in the therapy and diagnosis of various types of oncological diseases,” says Olena Komedchikova, a graduate student of the Laboratory of Biochemical Research of Carcinogenesis of the Moscow State University, the first author of the work.

The research was carried out with the financial support of the Ministry of Education and Science of the Russian Federation (projects No. 075-03-2023-106, FSMG-2023-0015 and FSMG-2023-0017) and the Russian Science Foundation (No. 19-14-00112 and No. 2241-13).

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