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

authored by: 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.
Organisation(s): Institute of Organic Chemistry
Institute of Inorganic Chemistry
External Organisation(s): Helmholtz Centre for Infection Research (HZI)
Hannover Medical School (MHH)
Type: Article
Journal: Journal of controlled release
Volume: 294
Pages: 327-336
No. of pages: 10
ISSN: 0168-3659
Publication date: 28.01.2019
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Pharmaceutical Science
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): http://hdl.handle.net/10033/621629 (Access: Open)
https://doi.org/10.1016/j.jconrel.2018.12.040 (Access: Closed)