Nanotheranostics 2021; 5(3):362-377. doi:10.7150/ntno.59458

Research Paper

Biodegradable polyelectrolyte/magnetite capsules for MR imaging and magnetic targeting of tumors

Yulia Svenskaya1✉*, Francesca Garello2*, Ekaterina Lengert1, Anastasiia Kozlova3, Roman Verkhovskii3, Valeria Bitonto2, Maria Rosaria Ruggiero2, Sergey German4,5, Dmitry Gorin5, Enzo Terreno2✉

1. Remote Controlled Systems for Theranostics laboratory, Research and Educational Institute of Nanostructures and Biosystems, Saratov State University, 410012 Saratov, Russia.
2. Molecular and Preclinical Imaging Centres, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.
3. Biomedical Photoacoustics Laboratory, Saratov State University, 410012 Saratov, Russia.
4. Laboratory of Optics and Spectroscopy of Nanoobjects, Institute of Spectroscopy of the RAS, Troitsk 108840, Russia.
5. Center of Photonics and Quantum Materials, Skolkovo Institute of Science and Technology, 143026 Moscow, Russia.
* Yu. Svenskaya and F. Garello contributed equally to this work.

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Citation:
Svenskaya Y, Garello F, Lengert E, Kozlova A, Verkhovskii R, Bitonto V, Ruggiero MR, German S, Gorin D, Terreno E. Biodegradable polyelectrolyte/magnetite capsules for MR imaging and magnetic targeting of tumors. Nanotheranostics 2021; 5(3):362-377. doi:10.7150/ntno.59458. Available from https://www.ntno.org/v05p0362.htm

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Abstract

Rationale: The tireless research for effective drug delivery approaches is prompted by poor target tissue penetration and limited selectivity against diseased cells. To overcome these issues, various nano- and micro-carriers have been developed so far, but some of them are characterized by slow degradation time, thus hampering repeated drug administrations. The aim of this study was to pursue a selective delivery of magnetic biodegradable polyelectrolyte capsules in a mouse breast cancer model, using an external magnetic field.

Methods: Four different kinds of magnetic polyelectrolyte capsules were fabricated via layer-by-layer assembly of biodegradable polymers on calcium carbonate templates. Magnetite nanoparticles were embedded either into the capsules' shell (sample S) or both into the shell and the inner volume of the capsules (samples CnS, where n is the number of nanoparticle loading cycles). Samples were first characterized in terms of their relaxometric and photosedimentometric properties. In vitro magnetic resonance imaging (MRI) experiments, carried out on RAW 264.7 cells, allowed the selection of two lead samples that proceeded for the in vivo testing on a mouse breast cancer model. In the set of in vivo experiments, an external magnet was applied for 1 hour following the intravenous injection of the capsules to improve their delivery to tumor, and MRI scans were acquired at different time points post administration.

Results: All samples were considered non-cytotoxic as they provided more than 76% viability of RAW 264.7 cells upon 2 h incubation. Sample S appeared to be the most efficient in terms of T2-MRI contrast, but the less sensitive to external magnet navigation, since no difference in MRI signal with and without the magnet was observed. On the other side, sample C6S was efficiently delivered to the tumor tissue, with a three-fold T2-MRI contrast enhancement upon the external magnet application. The effective magnetic targeting of C6S capsules was also confirmed by the reduction in T2-MRI contrast in spleen if compared with the untreated with magnet mice values, and the presence of dense and clustered iron aggregates in tumor histology sections even 48 h after the magnetic targeting.

Conclusion: The highlighted strategy of magnetic biodegradable polyelectrolyte capsules' design allows for the development of an efficient drug delivery system, which through an MRI-guided externally controlled navigation may lead to a significant improvement of the anticancer chemotherapy performance.

Keywords: magnetically-guided drug delivery systems, polyelectrolyte submicron capsules, magnetite nanoparticles, magnetic resonance imaging, targeted drug delivery.