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 penetra
Schematic representation of asialoglycoprotein receptor-mediated delivery and cell damage by AS-FrFeAG nanoparticles at a low alternating magnetic field. Due to a magnetic moment (M) of nanoparticles, they oscillate in an alternating magnetic field. AS-FrFeAG binds to fibronectin via aptamer AS-14 and disrupts extracellular matrix; AS-FrFeAG is internalized via asialoglycoprotein receptors and binds to Hsc70 via aptamer AS-42 causing lysosome damage and leakage of proteolytic enzymes resulting in cell lysis.
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