Vessel visualization and inhibition of tumor growth after injection of nanosystems based on magnetic nanoparticles modified by serum albumin with free radical approach

BACKGROUND: Nanosystems based on magnetic nanoparticles (MNPs) of iron oxides coated with human serum albumin (HSA) have a set of unique characteristics that make their use promising in the diagnosis and treatment of tumors. AIM: To investigate, using in vitro and in vivo models, the possibilities of using the systems we developed based on MNPs magnetite, modified by HSA using the free radical method, for contrasting tumors and slowing their growth. MATERIALS AND METHODS: The stability and integrity of the albumin coating formed on synthesized nanoparticles as a result of protein adsorption and fixation of adsorbed albumin molecules on nanoparticles due to modification of albumin by the action of a hydroxyl radical formed in a Fenton-like reaction was controlled by a change in the apparent optical density by 450 nm with the addition of immunoglobulin G. After in vitro confirmation of the contrasting properties and possible consequences of the contact of MNPs and nanosystems with blood by agglutination test, nanosystems containing MNPs and HSA were injected intraarterially into tumors implanted in rats at a dose of 20–60 μg per animal and the contrasting properties were studied in vivo using radiography and computed tomography. The effect of nanosystems on the tumor was assessed by the tumor growth index (TGI) and by the results of a pathomorphological study. RESULTS: To obtain nanosystems, joint incubation of MNPs and HSA was carried out for 24 hours in the presence of hydrogen peroxide, then subjected to magnetic separation. The stability and integrity of the protein coatings were confirmed with the addition of immunoglobulin G. In vitro studies have shown that the resulting nanosystem preparation in an aqueous medium with a MNPs concentration of 200 μg/ml does not lead to agglutination of blood cells and has a pronounced contrast. Vascular contrast in vivo, recorded 30 minutes after intraarterial administration, persisted for 14 days of follow-up. The tolerability study did not reveal any adverse side effects. With the introduction of nanosystems, a significant inhibition of tumor growth was noted compared with the control groups (p ≤0.05). Thus, tumors without the introduction of nanosystems reached a volume of 95,726.9±38,040.3 mm3 during the observation period — the TGI was 11±4.5. In the groups of rats treated with nanosystems at a dose of 20 micrograms of MNPs, tumors grew to 49,801±6011.2 mm3 (TGI 4.7±0.5), at a dose of 40 μg of MNPs — to 54,670.2±17 983.4 mm3 (IPO 5.5±1.4), at a dose of 60 μg of MNPs — to 43,342.5±14,637.2 mm3 (TGI 4.5±1.3). CONCLUSION: The steady contrast of tumor vessels with the introduction of nanosystems based on MNPs and HSA and their cytotoxic effect on the tumor is shown, which gives reason to consider the nanosystems developed by us promising for tumor theranostics.