Highly magnetic drug delivery vehicles for vital systems

Abstract: 

The development of targeted drug delivery technologies began with the production of polymer nanocomposite carriers [1]. Pioneering work was devoted to the search for polymers, proteins, enzymes that would encapsulate drugs with the highest efficiency, and also respond to external applied remote physical effects (ultrasound, light, electromagnetic radiation, magnetic and electric fields) [2,3,4]. At the same time, the interest of researchers gradually shifted towards minimizing the size and simultaneously increasing the efficiency of drug delivery, the amount of feedback to an external trigger. In vitro studies on cell lines of various etymologies were transferred to in vivo biological objects. Currently, the most promising non-invasive method for localizing magnetic carriers in a vessel, artery or vein, is a localized magnetic field [5]. It was shown for the first time in the work that polymer nanostructured micro-sized carriers can be retained inside the artery with high efficiency [6]. Theranostics of tumor diseases for such carriers is provided by both the drugs themselves, which are incorporated into the carrier, and magnetic nanoparticles, which have a contrast in both MRI modes simultaneously and can be agents for magnetic hyperthermia [7]. Reducing the size of the carrier can be achieved both by thermal collapse of the shell of the polymeric spherical capsules, and by reducing the size of the initial template, which is used to obtain carriers [8]. However, carriers of the type of mineral submicron core - protein-tannin shell have shown their advantage over widespread capsules [9]. In this work, we managed not only to effectively retain cytostatics for a long time in the carrier, but also to achieve depo systems based on these particles. In this case, the activity of carriers against breast cancer cell lines was shown due to the recrystallization of submicron mineral particles within the cell lines and the release of a cytostatic.

Separately, I would like to note that in the report not a little attention will be paid to label-free technologies for visualizing carriers in organs, tissues, cells by registering oscillations on magnons using Brillouin spectroscopy. A new biological application of the classical physical method for characterizing thin films makes it possible to visualize, and, most importantly, simultaneously record the magnetic and biomechanical properties of carriers and objects in vitro, ex vivo [10].

1. De Cock, L. J., De Koker, S., De Geest, B. G., Grooten, J., Vervaet, C., Remon, J. P., ... & Antipina, M. N. (2010). Polymeric multilayer capsules in drug delivery. Angewandte Chemie International Edition, 49(39), 6954-6973.

2. Bédard, M. F., De Geest, B. G., Skirtach, A. G., Möhwald, H., & Sukhorukov, G. B. (2010). Polymeric microcapsules with light responsive properties for encapsulation and release. Advances in colloid and interface science, 158(1-2), 2-14.

3. Lensen, D., Gelderblom, E. C., Vriezema, D. M., Marmottant, P., Verdonschot, N., Versluis, M., ... & Van Hest, J. C. (2011). Biodegradable polymeric microcapsules for selective ultrasound-triggered drug release. Soft Matter, 7(11), 5417-5422.

4. Voronin, D. V., Sindeeva, O. A., Kurochkin, M. A., Mayorova, O., Fedosov, I. V., Semyachkina-Glushkovskaya, O., ... & Sukhorukov, G. B. (2017). In vitro and in vivo visualization and trapping of fluorescent magnetic microcapsules in a bloodstream. ACS applied materials & interfaces, 9(8), 6885-6893.

5. Vidiasheva, I. V., Abalymov, A. A., Kurochkin, M. A., Mayorova, O. A., Lomova, M. V., German, S. V., ... & Sukhorukov, G. B. (2018). Transfer of cells with uptaken nanocomposite, magnetite-nanoparticle functionalized capsules with electromagnetic tweezers. Biomaterials science, 6(8), 2219-222