Iron oxide nanoparticles (NP) represent a promising theranostic platform for combined radiotherapy: the sensitized activity of iron oxide associated with ionizing irradiation enhances oxidative stress while magnetic properties may provide additional features as controlled therapeutics delivery.
In this study the sensitizing efficacy of nanosized metal-organic frameworks (nMOF) composed of Fe3O4 magnetic core double-coated with carboxymethyl - dextran sodium salt (CMD) and polyethyleneimine (PEI) was tested on C. elegans animal model, which were exposed subsequently to X-ray irradiation. nMOF used in the range from 0.016 µg/mL to 10 mg/mL alone, or in combination with 1, 3, 5, 7, 10 and 15 Gy irradiation. The nMOF delivery to E. coli OP50 and its further allocation within C elegans body were confirmed by Prussian blue staining.
nMOF alone in the range 10 μg/mL - 10 mg/mL exhibited geroprotective effect for C. elegans over 30 days of the experiment, in contrast to the toxic effect at low 0.016-10 μg/mL, compared to the control intact nematodes. C. elegans irradiation with 10 Gy showed the most toxic effect (decreased survival rate from 39 to 56%) after treatment of nematodes with 0.016-2 μg/mL nMOF, while at 15 Gy the C. elegans survival was in average on 13% higher, compared to control intact nematodes. Testing the low irradiation doses showed the dose-dependent effect of nMOF on nematodes survival. Spectrophotometric method showed that 66% of E. coli OP50 bacteria at 10 µg/mL nMOF after 24 hours of incubation irreversibly bind to bacteria. The penetration of nanoparticles into the digestive tract of nematodes was confirmed by microscope analysis of fixed nematodes after Prussian blue staining.
Our study has shown that the greatest lytic effect of C. elegans is the combination of 0.4 μg/mL nMOF with 1 Gy irradiation, which lead to 44% reduction of nematodes population compared to intact animals.
The studies were supported by the Russian Science Foundation (project No. 24-45-20002).
