image: Left: Schematic representation of silicon nanoparticles (SiNPs) biodegradation processes: (I) localization of SiNPs on the cell membrane; (II) penetration of SiNPs in the cytoplasm with partial solubility of the nanoparticles; (III) strong dissolution of SiNPs after 10-13 days within the cell body. Right: Raman spectra of SiNPs for different incubation times: 9 h, 48 h and 13 days of incubation depicted in red, blue and green, respectively. Inset: corresponding xz-cross-section of Raman spectroscopy images of MCF-7 cells cultivated with SiNPs. view more
Credit: Source: Lubov Osminkina
The Lomonosov Moscow State University researchers in collaboration with their German colleagues have succeeded in proving that silicon nanoparticles can be applied to diagnose and cure cancer. For the first time the ability of particles to penetrate into the diseased cells effectively and dissolve completely after delivering the drug was shown. The details of the research are presented in the article published in the latest issue of Nanomedicine: Nanotechnology, Biology and Medicine. http://dx.doi.org/10.1016/j.nano.2016.04.004
The scientific direction of the team is called theranostics. This term means a combined 'therapy' and 'diagnostics', denoting the process of simultaneous detection and treatment of the disease. One of its applications is spotting a range of oncologic diseases with the help of nanoparticles filled with medicine for their targeted delivery into a cancer cell. Nowadays a lot of such nanoparticles do not meet the requirement of biocompatibility. According to one of the researchers, Liubov Osminkina (senior research fellow, Physics Department of Lomonosov Moscow State University), some of the nanoparticles can act quickly, deliver the drug accurately, cure a number of diseases, but months later a patient may suffer from liver, kidney, lung pains, or even headache.
'The reason is that gold, silver, titanium oxide, cadmium selenide and a plenty of other nanoparticles are almost not excreted,' Liubov Osminkina explains. 'When nanoparticles reach the bloodstream, they can get stuck in internal organs and after a while they begin to harm the organism due to prolonged toxic effects.'
Searching not only biocompatible, but also bio-degradable transportation for a targeted drug delivery scientists noticed porous silicon. Its nano-particles would certainly do no harm, rather may help the organism, as the result of their dissolution is silicic acid, vital for bones and connective tissues.
These nanoparticles were Liubov Osminkina's main concern when she received the DAAD-MSU "Vladimir Vernadsky" grant in 2013 (a joint program for research by Moscow State University and the German Academic Exchange Service DAAD) for synthesizing photoluminescent nanoparticles of porous silicon nanowires for theranostics. She went to Jena, the Leibniz Institute of Photonic Technology one of the main scientific directions of which is biophotonics -- the use of optical techniques for studying living systems. The particular attention of a young employee of Moscow State University was focused on the Raman micro-spectroscopy.
The Raman spectroscopy is based on the aptitude of molecules to a so-called inelastic scattering of monochromatic light that is accompanied by a change of their internal state and thus a change of the frequency response of the emitted photons. This type of spectroscopy distinguishes the relative simplicity and the abundance of the information obtained -- enough to illuminate a material with a laser and analyze the spectrum of the radiation. Raman micro-spectroscopy was used at the Institute of Photonic Technology, among many other optical methods. With its help, scientists scanned the contents of a living cell and comparing the spectra obtained lined up a picture of what and where is located inside the cell.
'That's when I came up with an idea to conduct a study of nanoparticle biodegradation using Raman micro-spectroscopy,' the scientist says. 'This technique makes possible not only to locate the nanoparticles in the cell (the signals from the silicon and cell components have different frequencies), but also to watch the process of their disintegration. The latter was possible because, as already known, the Raman spectrum of silicon nanoparticles depends on their size - the smaller they are, the broader the spectrum becomes, shifting to lower frequencies'
Upon successful completion of the grant study, Osminkina won another DAAD-MSU grant which was for the implementation of her new ideas -- and she went to Jena again. The essence of Osminkina and her colleagues' new study came to the fact that the breast cancer cells were incubated with silicon nanoparticles of the 100 nm in size, and then, in particular, with the Raman micro-spectrometer, scientists have observed what happens in the cells during different periods of time from 5 hours to 13 days. Taking into account Raman spectrum and the reconstructed images of these particles and the cells they saw how during the first 5-9 hours nanoparticles localize on the cell membranes and penetrate into the cell during the next day and then begin to biodegrade, as evidenced by a decrease in signal amplitude, spectral broadening and the appearance of the peak of the amorphous silicon phase. It was shown that on the 13th day the nanoparticles dissolve completely and the signal disappears.
"Thus, for the first time we have shown that porous silicon nanoparticles could be completely harmless theranostics agents for many types of cancer. They do not only easily penetrate into the diseased cell, but when filled with drug, can emit it during their dissolving. I believe that the results of our work are of great importance in the long term as the basis for creating drugs based on biocompatible and biodegradable silicon nanoparticles,' Lubov Osminkina says.
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