How safe are upconversion nanoparticles?
MIPT tested the safety of the "magic bullet" against cancer
MIPT scientists and their colleagues from Moscow, Nizhny Novgorod, Australia and the Netherlands conducted the first systematic study of the safety of so–called upconversion nanoparticles in the treatment of skin cancer and other skin diseases - this work is one of the most important steps towards new, much more effective and safe methods of therapy and diagnosis of oncological diseases.
Fluorescent nanoparticles in cells (here and below are images from the MIPT press release)
Back in 1908, the German naturalist and physician Paul Ehrlich formulated the idea of a "magic bullet" – a medicine that would affect only pathogenic microbes or cancer cells, but would not affect healthy cells. A century later, thanks to nanotechnology, chemists and doctors are already close to getting such "bullets".
As it turned out, nanoparticles of some substances, entering the body, are able to selectively accumulate only in tumor cells, "ignoring" healthy ones. Molecules of drugs or diagnostic substances can be attached to such nanoparticles in order to find cancer cells and destroy them without damaging the rest of the body's cells.
In this role, in particular, gold nanoparticles, ferromagnets are used (they are heated with high-frequency currents, and they affect cancer cells from the inside). One of the types of nanoparticles that are considered the most promising for the diagnosis and treatment of cancerous tumors is the so–called upconverting nanophosphores (upconversion nanoparticle – UCNP). They are capable of "converting", that is, converting near-infrared radiation, capable of penetrating deep into the tissues of the human body, into visible light. Due to this, it is possible to detect cancer cells in the tissues of the body and influence them, monitoring the course of treatment. Upconversion nanoparticles can be configured in such a way that, under the influence of light, they will release medicinal substances.
However, before creating therapeutic methods based on the use of such nanoparticles, it is necessary to find out how harmless they are to healthy cells – this is the topic of the work of the group of Elena Petersen and Inna Trusova from MIPT and their colleagues from Moscow, Nizhny Novgorod, Australia and the Netherlands.
"Despite the fact that there are a large number of works concerning the cytotoxicity of upconversion nanoparticles, all of them are in a certain sense random in nature, since this task was side for them. For the first time, we conducted a systematic study of the effects of nanoparticles on cells," says study co–author Elena Petersen, head of the Laboratory of Cellular and Molecular Technologies at MIPT.
The scientists studied the properties of one of the most "popular" types of upconversion nanoparticles created on the basis of sodium tetrafluoroittriate doped with rare earth elements – erbium and ytterbium. They tested how these nanoparticles are absorbed by human connective tissue cells – fibroblasts – and skin epidermis cells – keratinocytes, and also studied how nanoparticles affect the viability of these cells.
Schematic representation of upconversion nanoparticles with various coatings
The results of the study show that the cytotoxicity of upconversion nanoparticles depends on the type of cells. They are non-toxic to dermal fibroblasts and low-toxic to keratinocytes. At the same time, the toxicity to keratinocytes depends on the concentration of nanoparticles, which means that these cells can be used as a biological indicator to assess the safety of different types of upconversion nanoparticles.
In addition to the "naked" nanoparticles, the scientists tested several variants of polymer-coated nanoparticles. In these cases, the discrepancy between the reaction of fibroblasts and keratinocytes turned out to be even higher – for example, particles coated with polyethylenimine severely disrupted intracellular metabolism of keratinocytes, but did not affect fibroblasts. The scientists determined the type of polymer coating that made the nanoparticles the safest.
"This study is an important step towards the practical application of upconversion nanoparticles for the diagnosis and treatment of skin cancer and other skin diseases," says Petersen.
According to her, by now there are already some studies concerning the use of nanoparticles for the treatment of skin diseases, but for large-scale use it is necessary to prove their safety and effectiveness.
The study was funded by a mega grant from the Government of the Russian Federation and a grant from the Russian Foundation for Basic Research.
Article by A. Guller et al. Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells is published in the journal Nano Research.
Portal "Eternal youth" http://vechnayamolodost.ru28.04.2015