Aptamer-Conjugated Superparamagnetic Ferroarabinogalactan Nanoparticles for Targeted Magnetodynamic Therapy of Cancer

Olga S Kolovskaya; Tatiana N Zamay; Galina S Zamay; Vasily A Babkin; Elena N Medvedeva; Nadezhda A Neverova; Andrey K Kirichenko; Sergey S Zamay; Ivan N Lapin; Evgeny V Morozov; Alexey E Sokolov; Andrey A Narodov; Dmitri G Fedorov; Felix N Tomilin; Vladimir N Zabluda; Yulia Alekhina; Kirill A Lukyanenko; Yury E Glazyrin; Valery A Svetlichnyi; Maxim V Berezovski; Anna S Kichkailo

doi:10.3390/cancers12010216

Aptamer-Conjugated Superparamagnetic Ferroarabinogalactan Nanoparticles for Targeted Magnetodynamic Therapy of Cancer

Cancers (Basel). 2020 Jan 15;12(1):216. doi: 10.3390/cancers12010216.

Authors

Olga S Kolovskaya^{1

2}, Tatiana N Zamay², Galina S Zamay^{1

2}, Vasily A Babkin³, Elena N Medvedeva³, Nadezhda A Neverova³, Andrey K Kirichenko², Sergey S Zamay^{1

4}, Ivan N Lapin⁵, Evgeny V Morozov^{4

6}, Alexey E Sokolov^{4

7}, Andrey A Narodov², Dmitri G Fedorov⁸, Felix N Tomilin^{1

4

9}, Vladimir N Zabluda⁴, Yulia Alekhina¹⁰, Kirill A Lukyanenko^{1

2

11}, Yury E Glazyrin^{1

2}, Valery A Svetlichnyi⁵, Maxim V Berezovski¹², Anna S Kichkailo^{1

2}

Affiliations

¹ Federal Research Center "Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Science", 660036 Krasnoyarsk, Russia.
² Laboratory for Biomolecular and Medical Technologies, Faculty of Medicine, Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenecki, 660022 Krasnoyarsk, Russia.
³ Irkutsk Institute of Chemistry named after A.E. Favorsky, the Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia.
⁴ L.V. Kirensky Institute of Physics SB RAS-The Branch of Federal Research Center "Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences", 660036 Krasnoyarsk, Russia.
⁵ Laboratory of Advanced Materials and Technology, Tomsk State University, 634050 Tomsk, Russia.
⁶ Institute of Chemistry and Chemical Technology SB RAS-The Branch of Federal Research Center "Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences", 660036 Krasnoyarsk, Russia.
⁷ School of Engineering Physics and Radio Electronics, Siberian Federal University, 660041 Krasnoyarsk, Russia.
⁸ Research Center for Computational Design of Advanced Functional Materials (CD-FMat), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8568, Japan.
⁹ School of Non-Ferrous Metals and Materials Science, Siberian Federal University, 660041 Krasnoyarsk, Russia.
¹⁰ Faculty of Physics, Department of Magnetism, Lomonosov Moscow State University, 119991 Moscow, Russia.
¹¹ School of Fundamental Biology and Biotechnology, Siberian Federal University, 660041 Krasnoyarsk, Russia.
¹² Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

Abstract

Nanotechnologies involving physical methods of tumor destruction using functional oligonucleotides are promising for targeted cancer therapy. Our study presents magnetodynamic therapy for selective elimination of tumor cells in vivo using DNA aptamer-functionalized magnetic nanoparticles exposed to a low frequency alternating magnetic field. We developed an enhanced targeting approach of cancer cells with aptamers and arabinogalactan. Aptamers to fibronectin (AS-14) and heat shock cognate 71 kDa protein (AS-42) facilitated the delivery of the nanoparticles to Ehrlich carcinoma cells, and arabinogalactan (AG) promoted internalization through asialoglycoprotein receptors. Specific delivery of the aptamer-modified FeAG nanoparticles to the tumor site was confirmed by magnetic resonance imaging (MRI). After the following treatment with a low frequency alternating magnetic field, AS-FeAG caused cancer cell death in vitro and tumor reduction in vivo. Histological analyses showed mechanical disruption of tumor tissues, total necrosis, cell lysis, and disruption of the extracellular matrix. The enhanced targeted magnetic theranostics with the aptamer conjugated superparamagnetic ferroarabinogalactans opens up a new venue for making biocompatible contrasting agents for MRI imaging and performing non-invasive anti-cancer therapies with a deep penetrated magnetic field.

Keywords: aptamers; arabinogalactan; drug delivery; magnetic resonance imaging; magnetically induced cell disruption; magnetodynamic therapy; superparamagnetic ferroarabinogalactans.