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

Olga S Kolovskaya,Felix N Tomilin,Kirill A Lukyanenko,Anna S Kichkailo,Sergey S Zamay,Evgeny V Morozov,Tatiana N Zamay,Yury E Glazyrin,Maxim V Berezovski,Dmitri G Fedorov,Galina S Zamay,И Н Лапин ,Е Н Медведева ,V N Zabluda ,Yu A Alekhina ,N A Neverova ,A E Sokolov ,А К Кириченко ,В А Бабкин ,А А Народов ,V A Svetlichnyi

doi:10.3390/cancers12010216

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.

Highlights

Current advances in the synthesis of aptamer conjugates with various drugs, biopolymers, and even nanoparticles enable the number of research studies in biomedicine to be increased
The most common strategy for producing superparamagnetic particles of 10–20 nm in diameter involves aqueous precipitation of iron salts in situ [22,23,24]. Many polymeric materials, such as dextran, carboxymethylated dextran, carboxydextran, starch, PEG, AG, glycosaminoglycan, organic siloxane, and sulfonated styrene have been proposed for coating iron oxide nanoparticles [25,26]
In order to increase biocompatibility, superparamagnetic iron particles were synthesized in the polymer matrix of AG

Summary

Introduction

Current advances in the synthesis of aptamer conjugates with various drugs, biopolymers, and even nanoparticles enable the number of research studies in biomedicine to be increased. Big interest in the treatment of cancers is in the application of aptamer conjugates with nanostructures due to their high specificity for cancer cells and low toxicity for the whole organism [1,2]. Superparamagnetic particles are preferable to ferromagnetic because, in the absence of a magnetic field, they have no magnetic moment, and they act only when the magnetic field is applied. Such particles have been used for magnetic resonance imaging (MRI), hyperthermia induction, and mechanical destruction of cells

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Results

Conclusion