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- In a double bottle: particles in the form of dumbbells will find and "kill" the tumor simultaneously
In a double bottle: particles in the form of dumbbells will find and "kill" the tumor simultaneously
For the first time, scientists have synthesized gold and iron nanoparticles in the form of dumbbells, capable of destroying tumor cells under the influence of light, as well as glowing, indicating their location. Moreover, the signal about the location of the formation can potentially remain quite bright throughout the entire therapy. Thanks to this, the same agent highlights the boundaries of metastases, and immediately destroys cells without systemic chemistry, experts said. For more information about promising therapy— see the Izvestia article.
Why did scientists synthesize dumbbell particles?
For the first time, scientists from Lomonosov Moscow State University have been able to combine two functional molecules in a nanoparticle at once: one of them emits a glow, allowing cancer to be detected, and the other absorbs radiation in a different range and triggers the death of tumor cells by generating reactive oxygen species. To do this, the particle was shaped like a dumbbell.
Characteristics of the obtained nanoparticles
Such carriers attract the attention of scientists as a new method of drug delivery, scientists told Izvestia. Unlike traditional spherical nanoparticles, "dumbbell-shaped" structures allow simultaneous transport of several substances and combine their functions.
However, combining different compounds in one system can negatively affect their properties. In particular, the glow of one molecule, which is necessary for visualization and diagnosis, can be absorbed by another, which leads to a loss of therapeutic effect — in this case, the system actually turns into only a diagnostic platform. This feature makes it difficult to use dumbbell-like nanoparticles that carry drugs, for example, in imaging cancerous tumors. However, variants of such systems that preserve the effectiveness of the two conflicting components have not yet been developed.
Confocal imaging of colon cancer cells after incubation for 2 hours with the following systems: (a) nanoparticles with photosensitizer; (b) nanoparticles with fluorophore; (c) nanoparticles with photosensitizer and fluorophore (combined image); (d) nanoparticles with photosensitizer and fluorophore (excitation wavelength = 405 nm); (e) nanoparticles with photosensitizer and fluorophore (excitation wavelength = 642 nm); (scale segment of 50 microns)
The authors from Moscow State University synthesized nanoparticles from magnetite — iron oxide — and gold. A photosensitizer was "loaded" onto the magnetic surface, a compound that, under the influence of light, releases toxic reactive oxygen species that destroy cell membranes and DNA. The second gold surface was combined with a fluorophore, a "luminous molecule." The result is a system that can be used simultaneously for both therapeutic and diagnostic purposes.
Accumulating pointwise in the tumor, such systems show its location due to the glow of the fluorophore. By selecting nanoparticles in the form of a dumbbell, the researchers were able to spatially separate the functional components — the photosensitizer and the fluorophore. This made it possible to avoid losses in luminescence, while maintaining high therapeutic performance.
As a result, chemists obtained nanoparticles that could glow and at the same time kill cancer cells by releasing reactive oxygen species. To test the performance of the systems, the authors conducted studies on colon cancer cells.
"We have shown that dimeric nanoparticles in the form of dumbbells can combine light—sensitive compounds. They will find application in diagnostics and photodynamic therapy. In the future, we plan to use such systems with other cell lines and tissues, and other compounds, such as signaling ones, to "see" the effect on the ensemble of regenerative processes in nervous tissue," said Natalia Klyachko, Doctor of Chemical Sciences, Professor, Head of the Department of Chemical Enzymology at the Lomonosov Moscow State University Faculty of Chemistry.
Promising tumor therapy
The scientists also noted: Magnetic nanoparticle-based systems are important for the development of new controllable biomaterials that respond to an external magnetic field.
Cytotoxicity data (colon cancer cell line): nanoparticles with photosensitizer, nanoparticles with fluorophore and nanoparticles with photosensitizer and fluorophore
Of course, such nanoparticles should find their application in medicine and diagnostics, says Evgeny Smirnov, associate professor at the ITMO Scientific and Educational Center for Infochemistry. Firstly, the choice of materials initially assumes high biocompatibility: gold is chemically inert, and iron is a natural participant in many biological processes in the body. At the same time, the nanoscale of the particles (10-15 nm) ensures their effective penetration into tissues and accumulation in the tumor area.
— Secondly, the authors managed to solve the long—standing task of combining diagnosis and therapy in "one bottle": the fluorescent signal allows precise localization of the tumor, and activation of the photosensitizer with light triggers the destruction of cancer cells - literally within the framework of one procedure. Thirdly, the presence of a magnetic material significantly expands the therapeutic potential of the system: in addition to PDT, the same nanoparticles can be used for MRI imaging, magnetic hyperthermia and chemodynamic therapy, paving the way for more advanced treatment regimens," the specialist told Izvestia.
Project Manager Natalia Klyachko
The key advantage of the approach is the elimination of the effect of resonant energy transfer, noted molecular biologist Arina Kholkina. Previously, when the fluorophore and photosensitizer approached, the diagnostic signal was extinguished before reaching the detector. The dumbbell shape physically separated the acceptor and the donor, removing the conflict. This made it possible to increase the phototoxicity of the system by orders of magnitude: reactive oxygen species are generated more efficiently, and the tumor is visible throughout therapy.
— The prospect of such systems is minimally invasive theranostics: the same agent highlights the boundaries of metastases and immediately destroys cells without systemic chemistry. This is a step towards controlled cell death under optical control," she said.
Project participant Julia Chudosai
Specialists from the Russian National Research Medical University named after N.I. Pirogov, the University of Science and Technology MISIS, the Russian Technological University MIREA, the Moscow Scientific Research Oncological Institute named after P.A. Herzen and the Institute of Organoelement Compounds named after A.N. Nesmeyanov RAS also participated in the study.
The results of the study, supported by a grant from the Russian Science Foundation (RSF), are published in the journal Scientific Reports.
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