Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model

verfasst von
Sami Ullah, Katja Seidel, Sibel Türkkan, Dawid Peter Warwas, Tatyana Dubich, Manfred Rohde, Hansjörg Hauser, Peter Behrens, Andreas Kirschning, Mario Köster, Dagmar Wirth
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.

Organisationseinheit(en)
Institut für Organische Chemie
Institut für Anorganische Chemie
Externe Organisation(en)
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Medizinische Hochschule Hannover (MHH)
Typ
Artikel
Journal
Journal of controlled release
Band
294
Seiten
327-336
Anzahl der Seiten
10
ISSN
0168-3659
Publikationsdatum
28.01.2019
Publikationsstatus
Veröffentlicht
Peer-reviewed
Ja
ASJC Scopus Sachgebiete
Pharmazeutische Wissenschaften
Ziele für nachhaltige Entwicklung
SDG 3 – Gute Gesundheit und Wohlergehen
Elektronische Version(en)
http://hdl.handle.net/10033/621629 (Zugang: Offen)
https://doi.org/10.1016/j.jconrel.2018.12.040 (Zugang: Geschlossen)