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Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model.
Ullah, Sami Seidel, Katja Türkkan, Sibel Warwas, Dawid Peter Dubich, Tatyana Rohde, Manfred Hauser, Hansjörg Behrens, Peter Kirschning, Andreas Köster, Mario
Ullah, Sami
Seidel, Katja
Türkkan, Sibel
Warwas, Dawid Peter
Dubich, Tatyana
Rohde, Manfred
Hauser, Hansjörg
Behrens, Peter
Kirschning, Andreas
Köster, Mario
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2018-12-23
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Abstract
Targeted delivery of drugs is a major challenge in treatment of diverse diseases. Systemically administered drugs demand high doses and are accompanied by poor selectivity and side effects on non-target cells. Here, we introduce a new principle for targeted drug delivery. It is based on macrophages as transporters for nanoparticle-coupled drugs as well as controlled release of drugs by hyperthermia mediated disruption of the cargo cells and simultaneous deliberation of nanoparticle-linked drugs. Hyperthermia is induced by an alternating electromagnetic field (AMF) that induces heat from silica-coated superparamagnetic iron oxide nanoparticles (SPIONs). We show proof-of-principle of controlled release by the simultaneous disruption of the cargo cells and the controlled, AMF induced release of a toxin, which was covalently linked to silica-coated SPIONs via a thermo-sensitive linker. Cells that had not been loaded with SPIONs remain unaffected. Moreover, in a 3D co-culture model we demonstrate specific killing of associated tumour cells when employing a ratio as low as 1:40 (SPION-loaded macrophage: tumour cells). Overall, our results demonstrate that AMF induced drug release from macrophage-entrapped nanoparticles is tightly controlled and may be an attractive novel strategy for targeted drug release.
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en
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1873-4995
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Attribution-NonCommercial-ShareAlike 4.0 International