Exactly in the cage
Scientists have found a way to noninvasively release a drug from polymer carriers inside cancer cells
ITMO University Blog, Naked Science
The concept, which was developed by ITMO University researchers, is based on the interaction of resonant semiconductor iron oxide nanoparticles with light.
Resonant semiconductor nanoparticles can be locally heated by laser exposure and convert the resulting light into heat. If such resonant particles modify the shell of polymer containers (capsules), which are used as means for delivering bioactive substances to cells and irradiate them with a laser, then the deformation of polymer capsules and the remote release of drugs in the right place at the right time will occur due to heat. The study was published in the journal Laser and Photonics Reviews (Zograf et al., All‐Optical Nanoscale Heating and Thermometry with Resonant Dielectric Nanoparticles for Controllable Drug Release in Living Cells).
An international team of physicists, chemists and biologists worked on a study in the field of non-invasive disclosure of capsules with drugs in cancer cells using optical radiation. Scientists from ITMO University were responsible for the synthesis and optical characterization of iron oxide nanoparticles, French colleagues helped to compile a full range of characterizations of iron oxide structures, which is used as a semiconductor nanoparticle. Colleagues from China made it possible to visualize the process of opening capsules with the drug, and the staff of the First Medical University of St. Petersburg conducted biological experiments on the delivery of an antitumor drug to primary tumor cells.
Currently, there are antitumor drugs that are able to effectively fight malignant neoplasms. But, unfortunately, they are aimed not only at affected cells and tissues, but also at healthy ones. Therefore, new approaches are needed to fight cancer. One of these approaches is the delivery of drugs using micro- and nanoparticles, in which locally high concentrations of the drug are created in the tumor area with minimal systemic concentrations throughout the body.
The idea of drug delivery using nano- and microparticles is as follows: the particles loaded with the drug are injected into the body and accumulate in the tumor area. In order to release the drug noninvasively, it is necessary to make the carrier particles photosensitive. For this purpose, resonant semiconductor nanoparticles made of iron oxide can be used to modify polymer containers (capsules). Further, when the modified polymer containers are irradiated, the iron oxide nanoparticles will heat up and the drug will be released noninvasively.
Moreover, the advantage of iron oxide is that this material is not only an efficient nanoheater, but also a local nanothermometer. That is, when the particles are heated, the temperature can be controlled, thereby preventing excessive heating of healthy cells and tissues.
"We have tested our invitro drug delivery systems on stem and tumor cells. Stem cells in this experiment were used as a model of healthy cells, and tumor cells as a model of diseased cells. As a control, the cells were simply irradiated with a laser with the same parameters. As a result, the effect of the antitumor drug was directed against tumor cells when they were irradiated with a laser, while the toxicity of drugs was practically not observed in relation to healthy cells. The control cells also survived at the end of the experiment, which suggests that the tumor cells died as a result of the release of the drug. Thus, effective photosensitive systems were created to deliver drugs to cells," Mikhail Zyuzin said.
The developed systems for drug delivery to cells can be used as local nanothermometers, which makes them multifunctional. "Nanoparticles in this case act as converters of light into heat and at the same time as a thermometer. The fact is that it is extremely difficult to measure the temperature using traditional methods on such small objects. For example, there are different techniques that use dyes that, when a certain temperature is reached, burn out and stop shining.
But the problem is that this is not reusable thermometry, and it is also binary, that is, we can only understand: it is above some temperature or below - yes or no. There will be no specific indicators. And semiconductor nanoparticles effectively absorb light and convert it into heat. Because of this, the frequency of oscillation of the crystal lattice begins to change slightly, and otherwise light begins to scatter. Based on these changes, we can determine how much we have heated the particle, and also see this data on the spectrometer," explained Georgy Zograf.
The researchers intend to continue working and develop the results obtained. It is planned to conduct preclinical studies on laboratory animals in vivo next year.
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