Optimal acidity
The pH level of a cancer cell is the basis of a new targeted drug delivery system in oncotherapy
The research team of NUST MISIS, SibSMU and the Pirogov Russian National Research University found that the efficiency of penetration of magnetic nanoparticles with a drug into a tumor depends on the pH level of its microenvironment (tissues). The results of the study will help to create an oncotherapeutic agent of "exact hit" and are published in the international scientific journal Nanomedicine (Pershina et al., Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles).
Magnetic iron oxide nanoparticles have been used by scientists for quite some time as a promising platform for targeted drug delivery due to their large surface area and range of nanoscale sizes. They can be visualized in vivo (in a living organism) using magnetic resonance imaging (MRI) and ensure controlled release of the drug in the right place of the body due to an alternating magnetic field.
Nevertheless, it is still very difficult to selectively accumulate such magnetic nanoparticles in tumors after their introduction. To control the flow of inanimate particles more precisely, scientists supply them with various "additives" of biological nature – biopolymer shells, parts of molecules, peptides, etc. According to Maxim Abakumov, head of the Biomedical Nanomaterials laboratory at NUST MISIS, the most modern drug delivery systems are based on the use of nanoparticles that "know how" to respond to the tumor microenvironment. These are so-called biologically sensitive nanoparticles.
They are usually coated with biopolymers and connected to molecules that can cause some response of tissues or cells of the body (for example, binding to tumor cells or drug release) only under conditions specific to the tumor. It can be hypoxia or acidic pH. Thus, the work of the drug is precisely localized in the tumor.
A team of scientists from NUST MISIS, SibSMU, N.I. Pirogov RNIMU conducted a comprehensive study of pH-controlled delivery of magnetic nanoparticles modified with pHLIP (short peptide, protein compound of amino acids), which provides increased uptake of substances in cells only at low pH values. The experiments were conducted in vitro and in vivo (on a mouse model of breast cancer). To measure the pH of a tumor in vivo, an original method of measuring pH using a nanoprobe was used. It was used to assess the effect of the degree of acidity of the tumor on the accumulation of magnetic nanoparticles in the tumor.
"Our in vivo experiment showed that magnetic nanoparticles connected to pHLIP are retained about 3 times better in tumor tissue compared to conventional nanoparticles. Thus, we can conclude that the drug can be released from a blood vessel, reach the tumor zone with an acidic extracellular pH and bind to malignant cells, which is confirmed by histological analysis. It is noteworthy that although such a nanopreparation gets inside the tumor, the heterogeneity of the pH level in the tumor affects delivery, namely retention and accumulation in the tumor tissue," said Maxim Abakumov, co–author of the study, head of the Biomedical Nanomaterials laboratory at NUST MISIS, PhD.
According to the developer, the best absorption efficiency is achieved with a slightly acidic pH, which is characteristic of the tumor microenvironment. Currently, the team continues preclinical studies of the resulting drug delivery system.
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