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Abstract
Introduction. Copolymers with a polyimide or cellulose backbone and polymethacrylic acid side chains are considered as promising nanostructured materials for targeted drug delivery. In the study in vitro and in vivo accumulation in tumors was assessed for hybrid tri-component nanosystems based on selenium nanoparticles, graft copolymers with a polyimide (HTN-1) or cellulose (HTN-3) backbone and side chains of polymethacrylic acid, and the photosensitizer Radachlorin.
Materials and Methods. The accumulation and localization of HTN-1 and HTN-3 in tumor cells was assessed by fluorescence confocal microscopy in human muscle non-invasive bladder cancer cell cultures after 24 h incubation. The in vivo study was performed in BALB/c mice with intradermally inoculated Ehrlich tumors. Evaluation was performed using the Fluor i In Vivo fluorescence imaging system at 1, 2, 3, 4, 6 and 24 hours after intravenous administration of the test compounds. The tumor/body fluorescence signal contrast was assessed using the ImageJ software.
Results. Confocal image analysis revealed the accumulation of both nanosystems in the cytoplasm of malignant cells, which was comparable to the accumulation of Radachlorin. In the Ehrlich tumor in mice, the fluorescence intensity of the nanosystems and Radachlorin was higher than in the surrounding tissue 6 and 24 hours after intravenous administration. Tumor/tissue fluorescence contrast increased after administration with peak values of 1.4 at 4 hours for Radachlorin, 1.5 at 4-6 hours for HTN-1 and 1.4 at 6-24 hours for HTN-3. The increase in time to peak tumor/tissue contrast is due to the change in pharmacokinetic properties when Radachlorin is incorporated into the nanosystems.
Conclusion. Hybrid tri-component nanosystems with polymide or cellulose backbones accumulate efficiently in tumor cells and slow down clearance from the tumor. Therefore, the development of targeted drugs based on them appears to be a perspective for the treatment and diagnosis of oncological diseases.
References
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